<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2020-06-18</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001580063</issuerCik>
        <issuerName>PROGENITY, INC.</issuerName>
        <issuerTradingSymbol>PROG</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001329344</rptOwnerCik>
            <rptOwnerName>Stylli Harry</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O PROGENITY, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>4330 LA JOLLA VILLAGE DRIVE, SUITE 200</rptOwnerStreet2>
            <rptOwnerCity>SAN DIEGO</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92122</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>Chairman &amp; CEO</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>1005302</value>
                    <footnoteId id="F1"/>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>13213254</value>
                    <footnoteId id="F2"/>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Series B Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F3"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F3"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F3"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>181647</value>
                    <footnoteId id="F3"/>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.76</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F4"/>
            </exerciseDate>
            <expirationDate>
                <value>2030-02-05</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>478148</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Includes 239,074 restricted stock units (&quot;RSUs&quot;), 19,922 of which have vested. All unvested RSUs will vest in semi-annual installments, subject to the Reporting Person's continued service to the Issuer, beginning on February 15, 2021 and ending on February 15, 2024.</footnote>
        <footnote id="F2">Each share of Series A Preferred Stock is convertible into common stock on a one-for-3.207 basis into the number of shares of common stock shown in column 3 at any time at the holder's election, and will convert automatically immediately prior to the closing of the Issuer's initial public offering. The Series A Preferred Stock has no expiration date.</footnote>
        <footnote id="F3">Each share of Series B Preferred Stock is convertible into common stock on 0.162-for-one basis, into the number of shares of common stock shown in column 3 at any time at the holder's election, and will convert automatically immediately prior to the closing of the Issuer's initial public offering. The Series B Preferred Stock has no expiration date.  The conversion rate of the Series B Preferred Stock is subject to adjustment in the event that the public offering price per share of the Issuer's common stock is less than $16.68, pursuant to the Issuer's seventh amended and restated certificate of incorporation.</footnote>
        <footnote id="F4">This option represents a right to purchase a total of 478,148 shares of the Issuer's common stock, one quarter of which will vest on February 5, 2021, with the remaining three quarters vesting in equal monthly installments for the following three years, subject to the Reporting Person's continued service to the Issuer.</footnote>
    </footnotes>

    <remarks>Exhibit 24 - Power of Attorney</remarks>

    <ownerSignature>
        <signatureName>/s/ Clarke Neumann, Attorney-in-fact for Harry Stylli</signatureName>
        <signatureDate>2020-06-18</signatureDate>
    </ownerSignature>
</ownershipDocument>
