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Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL‐2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML‐CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax. Methods: In this phase 2 trial, patients with CML‐CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 was achieved. After 3 years of combination, patients were maintained on single‐agent dasatinib. The primary end point was the rate of major molecular response (MMR) by 12 months of combination. Results: Sixty‐five patients were treated. Their median age was 46 years (range, 23–73). By 12 months of combination, the MMR, MR4, and MR4.5 rates were 86%, 53%, and 45%, respectively. After a median follow‐up of 42 months, the 4‐year event‐free and overall survival rates were 96% and 100%, respectively. Outcomes with the combination were comparable to historical outcomes with single‐agent dasatinib (cumulative 12‐months MMR rate of 79% with both strategies). The incidence of grade 3‐4 neutropenia was 22% with the combination and 11% with single‐agent dasatinib (p <.001). Conclusions: Treatment with dasatinib and venetoclax was safe and effective in CML‐CP. The cumulative response rates with the combination were similar to those with single‐agent dasatinib. Further follow‐up is needed to evaluate the rates of durable deep molecular response and treatment‐free remission. Treatment with dasatinib and venetoclax was effective and well‐tolerated. By 12 months of combination, 86% and 53% of patients achieved a major molecular response and a deep molecular response, respectively. [ABSTRACT FROM AUTHOR]