Venetoclax (Ven), when combined with intensive chemotherapy, shows promise for untreated acute myeloid leukemia (AML), but its integration with the 7+3 regimen remains underexplored. In a phase 1b study, we assessed the safety and efficacy of Ven with daunorubicin and cytarabine in patients with newly diagnosed AML. A total of 34 patients (median age, 59 years; 62% non-White) received Ven at escalating durations (8, 11, or 14 days). Adverse events included febrile neutropenia (100%), sepsis (29%), and enterocolitis (23.5%), but there were no induction deaths. The median recovery times for neutrophils (>1.0 × 103/μL) and platelets (>100 × 103/μL) were less than 30 days. Composite complete remission was achieved in 85.3% of patients, and 86.2% were negative for measurable residual disease (MRD). Responses spanned all European Leukemia Net 2022 risk categories. With a median follow-up of 9.6 (2-20) months, the median duration of response, event-free survival, and overall survival were not reached. Ven (400 mg), when combined with 7+3 chemotherapy, was safe and effective in achieving MRD-negative remissions across all durations. Ven dose optimization is being explored in the expansion phase of this trial. Future multicenter studies should confirm our findings. This trial was registered at clinicaltrials.gov as #NCT05342584.