Inclusion Criteria:
* Confirmation of Acute myeloid leukemia (AML) diagnosis by World Health Organization (WHO) criteria, have a projected life expectancy of at least 12 weeks, previously untreated, and ineligible for treatment with intensive chemotherapy.
* Participant must be considered ineligible for induction therapy defined by the following:
* \>= 75 years of age
* \>=18 to 74 years of age with at least one of the following comorbidities:
* Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.
* Cardiac history of congestive heart failure requiring treatment or ejection fraction \<= 50% or chronic stable angina.
* Diffusing capacity of the lung for carbon monoxide (DLCO) \<= 65% or forced expiratory volume during the first second (FEV1) \<= 65%.
* Creatinine clearance \>= 30 mL/min to \< 45 mL/min.
* Moderate hepatic impairment with total bilirubin \> 1.5 to \<= 3.0 × upper limit of normal (ULN).
* Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy.
* Must meet the laboratory requirements per the protocol.
* Must have an ECOG performance status of:
* 0 to 2 for subject ≥ 75 year of age; or
* 0 to 3 for subject ≥ 18 to 74 years of age.
* Female participant must not be pregnant or breastfeeding and is not considering becoming pregnant or donating eggs during the study or for approximately six months after the last dose of study drug.
* Female participants of childbearing potential must agree to use at least 1 protocol-specified method of birth control and male participants, if sexually active with female partner(s) of childbearing potential, must agree to practice the protocol-specified contraception.
Exclusion Criteria:
* History of any malignancies within 2 years prior to study entry with exception noted in the protocol.
* Have received any investigational drug 30 days prior to the first dose of study drug.
* Have received strong and/or moderate CYP3A inducers within 7 days prior to initiation of study treatment.
* Must not have received treatment with the following:
* An hypomethylating agent (HMA), venetoclax, and/or any chemotherapeutic agent for myelodysplastic syndrome (MDS).
* Prior therapy or experimental therapies for MDS or Acute myeloid leukemia (AML).
* Current participation in another research or observational study.
* Myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, and AML with BCR-ABL1 translocation.
* Participant has acute promyelocytic leukemia.
* Participant has known active central nervous system (CNS) involvement with AML.
* Participant has a history of malabsorption syndrome or other condition that precludes enteral route of administration.
* Participant has known HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at Screening, only if required per local guidelines or institutional standards.
* Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with high viral titers. Participants with HBV inactive carrier status and/or HCV with low viral titers on antivirals (non-exclusionary medications) are eligible.
* Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
* Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
* Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
