Inclusion Criteria:

          -  Previously untreated participants with CD20-positive DLBCL.

          -  BCL-2 protein overexpression by IHC, as assessed by local testing.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.

          -  International Prognostic Index (IPI) 2-5.

          -  Life expectancy of more than 6 months.

          -  Left ventricular ejection fraction (LVEF) ≥ 50%, as determined on cardiac
             multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO).

          -  Availability of archival or freshly collected tumor tissue prior to study enrollment.

          -  At least one bi-dimensionally fluorodeoxyglucose-avid measurable lymphoma lesion on
             PET/CT scan, defined as > 1.5 cm in its longest dimension on CT scan.

          -  Adequate hematopoietic function.

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraception, and agreement to refrain from donating
             eggs.

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom, and agreement to refrain from donating sperm.

        Exclusion Criteria:

          -  Current diagnosis of unclassifiable B-cell lymphoma.

          -  Prior treatment for indolent lymphoma.

          -  Current Grade > 1 peripheral neuropathy.

          -  Prior organ transplantation.

          -  Prior use of any monoclonal antibody within 3 months and any investigational therapy
             within 28 days prior to the start of Cycle 1.

          -  Vaccination with live vaccines within 28 days prior to the start of Cycle 1.

          -  Prior therapy for DLBCL and High-Grade B-cell Lymphoma (HGBCL) with the exception of
             palliative, short-term treatment with corticosteroids.

          -  Recent major surgery (within 6 weeks prior to the start of Day 1 of Cycle 1), other
             than for diagnosis.

          -  History of other cancers within 2 years prior to screening.

          -  Any active infection that, in the opinion of the investigator, would impact
             participant safety within 7 days prior to Day 1 of Cycle 1.

          -  Serious infection requiring oral or IV antibiotics within 4 weeks prior to Day 1 of
             Cycle 1.

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the participant's safe participation in and
             completion of the study.

          -  Positive for Hepatitis B/C Viruses (HBV/HCV) and Human T-cell Leukemia Virus (HTLV)-1.

          -  Known infection with HIV.

          -  History of progressive multifocal leukoencephalopathy.

          -  Suspected active or latent tuberculosis.

          -  Clinically significant history of liver disease, including viral or other hepatitis or
             cirrhosis.

          -  Substance abuse, including non-prescription drug and alcohol dependence, within 12
             months prior to screening.

          -  Pregnant or breastfeeding, or intending to become pregnant during the study within 6
             months after the final dose of venetoclax, 9 months after the final dose of
             polatuzumab vedotin, or 12 months after the final dose of rituximab.

          -  History or presence of an abnormal ECG that is clinically significant in the
             investigator's opinion.

          -  Malabsorption syndrome or other condition that would interfere with enteral
             absorption.

          -  Blood transfusion within 14 days prior to screening.