Venetoclax is an emerging drug for the treatment of various types of blood cancers. It was first approved in 2016 for the treatment of relapsed and refractory chronic lymphocytic leukemia. Later, the indications expanded, and multiple research as well as clinical studies are still conducted involving venetoclax. No analytical method for the determination of venetoclax can currently be found in the literature. We developed a mass spectrometry-compatible stability-indicating ultrahigh-performance liquid chromatography (LC) method for venetoclax. The LC method was developed using analytical quality by design principles. The developed method is able to separate venetoclax and its degradation products. The method was validated in the working point where a linearity range was established and accuracy, repeatability, and selectivity were assessed. Venetoclax is the only Bcl-2 protein inhibitor on the market. It is very effective in combinational therapy, so future drug development involving venetoclax may be expected. A stability-indicating method could aid in the development of new pharmaceutical products with venetoclax.