<?xml version="1.0" encoding="utf-8"?>
<!--XBRL document created by Certent Disclosure Management 22.2.0.1 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/5/2022 5:30:11 PM-->
<!--Modified on: 5/5/2022 5:30:11 PM-->
<linkbase xmlns="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#StatementCondensedConsolidatedBalanceSheets" roleURI="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedBalanceSheets"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" roleURI="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#StatementCondensedConsolidatedStatementsOfCashFlows" roleURI="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedStatementsOfCashFlows"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureFinancialInstrumentSummaryOfAssetsAndLiabilitiesMeasuredAtFairValueOnRecurringBasisDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentSummaryOfAssetsAndLiabilitiesMeasuredAtFairValueOnRecurringBasisDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureFinancialInstrumentsSummaryOfCashCashEquivalentsAndInvestmentsDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentsSummaryOfCashCashEquivalentsAndInvestmentsDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureFinancialInstrumentsSummaryOfContractualMaturitiesOfCashEquivalentsAndAvailableForSaleInvestmentsDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentsSummaryOfContractualMaturitiesOfCashEquivalentsAndAvailableForSaleInvestmentsDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureBalanceSheetComponentsComponentsOfInventoryDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsComponentsOfInventoryDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureBalanceSheetComponentsDefiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsDefiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureBalanceSheetComponentsEstimatedFutureAmortizationExpenseOfAcquisitionRelatedIntangibleAssetsWithDefiniteLivesDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsEstimatedFutureAmortizationExpenseOfAcquisitionRelatedIntangibleAssetsWithDefiniteLivesDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureBalanceSheetComponentsFurturePrincipalPaymentsDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsFurturePrincipalPaymentsDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureConvertibleSeniorNotesScheduleOfNetCarryingAmountDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureConvertibleSeniorNotesScheduleOfNetCarryingAmountDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureConvertibleSeniorNotesScheduleOfInterestExpenseDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureConvertibleSeniorNotesScheduleOfInterestExpenseDetails"></roleRef>
  <roleRef xlink:type="simple" xlink:href="pacb-20220331.xsd#DisclosureNetLossPerShareComputationOfBasicAndDilutedNetLossPerShareDetails" roleURI="http://www.pacificbiosciences.com/role/DisclosureNetLossPerShareComputationOfBasicAndDilutedNetLossPerShareDetails"></roleRef>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedBalanceSheets" xlink:type="extended" xlink:title="00100 - Statement - Condensed Consolidated Balance Sheets">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Assets" xlink:label="us-gaap_Assets"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsCurrent" xlink:label="us-gaap_AssetsCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_AssetsCurrent_637873686087175626" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue" xlink:label="us-gaap_CashAndCashEquivalentsAtCarryingValue_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_CashAndCashEquivalentsAtCarryingValue_637873686087175626" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShortTermInvestments" xlink:label="us-gaap_ShortTermInvestments_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_ShortTermInvestments_637873686087175626" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableNetCurrent" xlink:label="us-gaap_AccountsReceivableNetCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_AccountsReceivableNetCurrent_637873686087175626" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_InventoryNet_637873686087175626" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent" xlink:label="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_PrepaidExpenseAndOtherAssetsCurrent_637873686087175626" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashCurrent" xlink:label="us-gaap_RestrictedCashCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsCurrent_637873686087175626" xlink:to="us-gaap_RestrictedCashCurrent_637873686087175626" order="6" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_637873686087175626" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset" xlink:label="us-gaap_OperatingLeaseRightOfUseAsset_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OperatingLeaseRightOfUseAsset_637873686087175626" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedCashAndCashEquivalentsNoncurrent" xlink:label="us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_637873686087175626" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="us-gaap_OtherAssetsNoncurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_OtherAssetsNoncurrent_637873686087175626" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwill_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_IntangibleAssetsNetExcludingGoodwill_637873686087175626" order="6" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Assets" xlink:to="us-gaap_Goodwill_637873686087175626" order="7" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Liabilities" xlink:label="us-gaap_Liabilities_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_Liabilities_637873686087175626" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LiabilitiesCurrent" xlink:label="us-gaap_LiabilitiesCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_LiabilitiesCurrent_637873686087175626" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsPayableCurrent" xlink:label="us-gaap_AccountsPayableCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637873686087175626" xlink:to="us-gaap_AccountsPayableCurrent_637873686087175626" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccruedLiabilitiesCurrent" xlink:label="us-gaap_AccruedLiabilitiesCurrent_637873686087175626"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637873686087175626" xlink:to="us-gaap_AccruedLiabilitiesCurrent_637873686087175626" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637873686087175626" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_637873686087186006" order="3" use="optional" weight="1" priority="1"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityCurrent" xlink:label="us-gaap_OperatingLeaseLiabilityCurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637873686087175626" xlink:to="us-gaap_OperatingLeaseLiabilityCurrent_637873686087186006" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesCurrent" xlink:label="us-gaap_OtherLiabilitiesCurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesCurrent_637873686087175626" xlink:to="us-gaap_OtherLiabilitiesCurrent_637873686087186006" order="5" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_637873686087186006" order="2" use="optional" weight="1" priority="1"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent" xlink:label="us-gaap_OperatingLeaseLiabilityNoncurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_OperatingLeaseLiabilityNoncurrent_637873686087186006" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConvertibleLongTermNotesPayable" xlink:label="us-gaap_ConvertibleLongTermNotesPayable_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_ConvertibleLongTermNotesPayable_637873686087186006" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherLiabilitiesNoncurrent" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_OtherLiabilitiesNoncurrent_637873686087186006" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_Liabilities_637873686087175626" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiabilityNoncurrent_637873686087186006" order="6" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_StockholdersEquity_637873686087186006" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockValue" xlink:label="us-gaap_PreferredStockValue_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637873686087186006" xlink:to="us-gaap_PreferredStockValue_637873686087186006" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockValue" xlink:label="us-gaap_CommonStockValue_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637873686087186006" xlink:to="us-gaap_CommonStockValue_637873686087186006" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapital" xlink:label="us-gaap_AdditionalPaidInCapital_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637873686087186006" xlink:to="us-gaap_AdditionalPaidInCapital_637873686087186006" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637873686087186006" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_637873686087186006" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_StockholdersEquity_637873686087186006" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_637873686087186006" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommitmentsAndContingencies" xlink:label="us-gaap_CommitmentsAndContingencies_637873686087186006"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_CommitmentsAndContingencies_637873686087186006" order="3" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" xlink:type="extended" xlink:title="00200 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax" xlink:label="us-gaap_ComprehensiveIncomeNetOfTax"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_NetIncomeLoss_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" xlink:label="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetIncomeLoss_637873686087195895" xlink:to="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="us-gaap_OtherNonoperatingIncomeExpense_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895" xlink:to="us-gaap_OtherNonoperatingIncomeExpense_637873686087195895" order="1" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpense" xlink:label="us-gaap_InterestExpense_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895" xlink:to="us-gaap_InterestExpense_637873686087195895" order="2" use="optional" weight="-1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnContractTermination" xlink:label="us-gaap_GainLossOnContractTermination_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895" xlink:to="us-gaap_GainLossOnContractTermination_637873686087195895" order="3" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss" xlink:label="us-gaap_OperatingIncomeLoss_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_637873686087195895" xlink:to="us-gaap_OperatingIncomeLoss_637873686087195895" order="4" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GrossProfit" xlink:label="us-gaap_GrossProfit_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_637873686087195895" xlink:to="us-gaap_GrossProfit_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax" xlink:label="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit_637873686087195895" xlink:to="us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfRevenue" xlink:label="us-gaap_CostOfRevenue_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_GrossProfit_637873686087195895" xlink:to="us-gaap_CostOfRevenue_637873686087195895" order="2" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSoldAmortization" xlink:label="us-gaap_CostOfGoodsAndServicesSoldAmortization_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostOfRevenue_637873686087195895" xlink:to="us-gaap_CostOfGoodsAndServicesSoldAmortization_637873686087195895" order="1" use="optional" weight="1" priority="4"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="us-gaap_CostOfGoodsAndServicesSold_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostOfRevenue_637873686087195895" xlink:to="us-gaap_CostOfGoodsAndServicesSold_637873686087195895" order="2" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherCostOfOperatingRevenue" xlink:label="us-gaap_OtherCostOfOperatingRevenue_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CostOfRevenue_637873686087195895" xlink:to="us-gaap_OtherCostOfOperatingRevenue_637873686087195895" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingExpenses" xlink:label="us-gaap_OperatingExpenses_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingIncomeLoss_637873686087195895" xlink:to="us-gaap_OperatingExpenses_637873686087195895" order="2" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense" xlink:label="us-gaap_ResearchAndDevelopmentExpense_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_637873686087195895" xlink:to="us-gaap_ResearchAndDevelopmentExpense_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SellingGeneralAndAdministrativeExpense" xlink:label="us-gaap_SellingGeneralAndAdministrativeExpense_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_637873686087195895" xlink:to="us-gaap_SellingGeneralAndAdministrativeExpense_637873686087195895" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_OperatingExpenses_637873686087195895" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_637873686087195895" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" xlink:label="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_ComprehensiveIncomeNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_637873686087195895" order="2" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/StatementCondensedConsolidatedStatementsOfCashFlows" xlink:type="extended" xlink:title="00500 - Statement - Condensed Consolidated Statements of Cash Flows">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:label="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="pacb-20220331.xsd#pacb_AmortizationOfIntangibleAssetsAndResearchDevelopmentExpense" xlink:label="pacb_AmortizationOfIntangibleAssetsAndResearchDevelopmentExpense_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="pacb_AmortizationOfIntangibleAssetsAndResearchDevelopmentExpense_637873686087195895" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss" xlink:label="us-gaap_NetIncomeLoss_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_NetIncomeLoss_637873686087195895" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnContractTermination" xlink:label="us-gaap_GainLossOnContractTermination_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_GainLossOnContractTermination_637873686087195895" order="3" use="optional" weight="-1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation" xlink:label="us-gaap_Depreciation_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_Depreciation_637873686087195895" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinanceLeaseRightOfUseAssetAmortization" xlink:label="us-gaap_FinanceLeaseRightOfUseAssetAmortization_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_FinanceLeaseRightOfUseAssetAmortization_637873686087195895" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts" xlink:label="us-gaap_AmortizationOfFinancingCostsAndDiscounts_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_AmortizationOfFinancingCostsAndDiscounts_637873686087195895" order="6" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GainLossOnSaleOfPropertyPlantEquipment" xlink:label="us-gaap_GainLossOnSaleOfPropertyPlantEquipment_637873686087195895"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_GainLossOnSaleOfPropertyPlantEquipment_637873686087195895" order="7" use="optional" weight="-1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensation" xlink:label="us-gaap_ShareBasedCompensation_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_ShareBasedCompensation_637873686087205535" order="8" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium" xlink:label="us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_InvestmentIncomeNetAmortizationOfDiscountAndPremium_637873686087205535" order="9" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsReceivable" xlink:label="us-gaap_IncreaseDecreaseInAccountsReceivable_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInAccountsReceivable_637873686087205535" order="10" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInInventories" xlink:label="us-gaap_IncreaseDecreaseInInventories_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInInventories_637873686087205535" order="11" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets" xlink:label="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_637873686087205535" order="12" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccruedLiabilities" xlink:label="us-gaap_IncreaseDecreaseInAccruedLiabilities_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInAccruedLiabilities_637873686087205535" order="13" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInAccountsPayable" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInAccountsPayable_637873686087205535" order="14" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInOtherCurrentLiabilities" xlink:label="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInOtherCurrentLiabilities_637873686087205535" order="15" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerAsset" xlink:label="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_IncreaseDecreaseInContractWithCustomerAsset_637873686087205535" order="16" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeasePayments" xlink:label="us-gaap_OperatingLeasePayments_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_OperatingLeasePayments_637873686087205535" order="17" use="optional" weight="-1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInOperatingActivities_637873686087195895" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_637873686087205535" order="18" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_637873686087205535" order="1" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PaymentsToAcquireInvestments" xlink:label="us-gaap_PaymentsToAcquireInvestments_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535" xlink:to="us-gaap_PaymentsToAcquireInvestments_637873686087205535" order="2" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt" xlink:label="us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535" xlink:to="us-gaap_ProceedsFromSaleOfAvailableForSaleSecuritiesDebt_637873686087205535" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities" xlink:label="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInInvestingActivities_637873686087205535" xlink:to="us-gaap_ProceedsFromMaturitiesPrepaymentsAndCallsOfAvailableForSaleSecurities_637873686087205535" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseExcludingExchangeRateEffect" xlink:to="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="pacb-20220331.xsd#pacb_ProceedsFromRepaymentsOfContractTermination" xlink:label="pacb_ProceedsFromRepaymentsOfContractTermination_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" xlink:to="pacb_ProceedsFromRepaymentsOfContractTermination_637873686087205535" order="1" use="optional" weight="1" priority="1"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RepaymentsOfNotesPayable" xlink:label="us-gaap_RepaymentsOfNotesPayable_637873686087205535"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" xlink:to="us-gaap_RepaymentsOfNotesPayable_637873686087205535" order="2" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromConvertibleDebt" xlink:label="us-gaap_ProceedsFromConvertibleDebt_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" xlink:to="us-gaap_ProceedsFromConvertibleDebt_637873686087215855" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock_637873686087215855" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromPaymentsForOtherFinancingActivities" xlink:label="us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_NetCashProvidedByUsedInFinancingActivities_637873686087205535" xlink:to="us-gaap_ProceedsFromPaymentsForOtherFinancingActivities_637873686087215855" order="5" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentSummaryOfAssetsAndLiabilitiesMeasuredAtFairValueOnRecurringBasisDetails" xlink:type="extended" xlink:title="40502 - Disclosure - Financial Instrument (Summary of Assets and Liabilities Measured at Fair Value on a Recurring Basis) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure_637873686087215855" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InvestmentsFairValueDisclosure" xlink:label="us-gaap_InvestmentsFairValueDisclosure_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="us-gaap_InvestmentsFairValueDisclosure_637873686087215855" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="pacb-20220331.xsd#pacb_ShortTermRestrictedCashFairValueDisclosure" xlink:label="pacb_ShortTermRestrictedCashFairValueDisclosure_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="pacb_ShortTermRestrictedCashFairValueDisclosure_637873686087215855" order="3" use="optional" weight="1" priority="1"></calculationArc>
    <loc xlink:type="locator" xlink:href="pacb-20220331.xsd#pacb_LongTermRestrictedCashFairValueDisclosure" xlink:label="pacb_LongTermRestrictedCashFairValueDisclosure_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AssetsFairValueDisclosure" xlink:to="pacb_LongTermRestrictedCashFairValueDisclosure_637873686087215855" order="4" use="optional" weight="1" priority="1"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentsSummaryOfCashCashEquivalentsAndInvestmentsDetails" xlink:type="extended" xlink:title="40504 - Disclosure - Financial Instruments (Summary of Cash, Cash Equivalents and Investments) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_637873686087215855" order="1" use="optional" weight="-1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_637873686087215855" order="2" use="optional" weight="1" priority="3"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecurities_637873686087215855" order="3" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureFinancialInstrumentsSummaryOfContractualMaturitiesOfCashEquivalentsAndAvailableForSaleInvestmentsDetails" xlink:type="extended" xlink:title="40505 - Disclosure - Financial Instruments (Summary of Contractual Maturities of Cash Equivalents and Available-for-Sale Investments) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecurities"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_637873686087215855" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtSecurities" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent_637873686087215855" order="2" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsComponentsOfInventoryDetails" xlink:type="extended" xlink:title="40602 - Disclosure - Balance Sheet Components (Components of Inventory) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryNet" xlink:label="us-gaap_InventoryNet_635888865099742422"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryRawMaterialsNetOfReserves" xlink:label="us-gaap_InventoryRawMaterialsNetOfReserves_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet_635888865099742422" xlink:to="us-gaap_InventoryRawMaterialsNetOfReserves_637873686087215855" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryWorkInProcessNetOfReserves" xlink:label="us-gaap_InventoryWorkInProcessNetOfReserves_637873686087215855"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet_635888865099742422" xlink:to="us-gaap_InventoryWorkInProcessNetOfReserves_637873686087215855" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryFinishedGoodsNetOfReserves" xlink:label="us-gaap_InventoryFinishedGoodsNetOfReserves_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InventoryNet_635888865099742422" xlink:to="us-gaap_InventoryFinishedGoodsNetOfReserves_637873686087225954" order="3" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsDefiniteLivedIntangibleAssetsFromBusinessAcquisitionsDetails" xlink:type="extended" xlink:title="40605 - Disclosure - Balance Sheet Components (Definite-lived Intangible Assets from Business Acquisitions) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_637873686087225954" order="1" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsGross" xlink:label="us-gaap_FiniteLivedIntangibleAssetsGross_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross_637873686087225954" order="2" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsEstimatedFutureAmortizationExpenseOfAcquisitionRelatedIntangibleAssetsWithDefiniteLivesDetails" xlink:type="extended" xlink:title="40606 - Disclosure - Balance Sheet Components (Estimated Future Amortization Expense Of Acquisition-Related Intangible Assets With Definite Lives) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseAfterYearFive_637873686087225954" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseRemainderOfFiscalYear_637873686087225954" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearFour_637873686087225954" order="3" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseNextTwelveMonths_637873686087225954" order="4" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearThree_637873686087225954" order="5" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNet" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAmortizationExpenseYearTwo_637873686087225954" order="6" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureBalanceSheetComponentsFurturePrincipalPaymentsDetails" xlink:type="extended" xlink:title="40608 - Disclosure - Balance Sheet Components (Furture Principal Payments) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_637873686087225954" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_637873686087225954" order="2" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_637873686087225954" order="3" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureConvertibleSeniorNotesScheduleOfNetCarryingAmountDetails" xlink:type="extended" xlink:title="40702 - Disclosure - Convertible Senior Notes (Schedule of Net Carrying Amount) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LongTermDebt" xlink:label="us-gaap_LongTermDebt"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet" xlink:label="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_637873686087225954" order="1" use="optional" weight="-1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DebtInstrumentCarryingAmount" xlink:label="us-gaap_DebtInstrumentCarryingAmount_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_LongTermDebt" xlink:to="us-gaap_DebtInstrumentCarryingAmount_637873686087225954" order="2" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureConvertibleSeniorNotesScheduleOfInterestExpenseDetails" xlink:type="extended" xlink:title="40703 - Disclosure - Convertible Senior Notes (Schedule of Interest Expense) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InterestExpenseDebt" xlink:label="us-gaap_InterestExpenseDebt"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AmortizationOfFinancingCosts" xlink:label="us-gaap_AmortizationOfFinancingCosts_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InterestExpenseDebt" xlink:to="us-gaap_AmortizationOfFinancingCosts_637873686087225954" order="1" use="optional" weight="1" priority="2"></calculationArc>
    <loc xlink:type="locator" xlink:href="pacb-20220331.xsd#pacb_ContractualInterestExpense" xlink:label="pacb_ContractualInterestExpense_637873686087225954"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_InterestExpenseDebt" xlink:to="pacb_ContractualInterestExpense_637873686087225954" order="2" use="optional" weight="1" priority="2"></calculationArc></calculationLink>
  <calculationLink xlink:role="http://www.pacificbiosciences.com/role/DisclosureNetLossPerShareComputationOfBasicAndDilutedNetLossPerShareDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Net Loss Per Share (Computation Of Basic And Diluted Net Loss Per Share) (Details)">
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"></loc>
    <loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_637873686087235472"></loc>
    <calculationArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_637873686087235472" order="1" use="optional" weight="1" priority="2"></calculationArc></calculationLink></linkbase>
