Venetoclax is a potent BCL-2 inhibitor that is used for the treatment of several blood cancers. During the oxidative stress degradation of venetoclax, we observed the formation of two potential impurities at levels of about 8−10%, which have similar molecular weights. The two impurities were isolated and identified as 4- (3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4- (((3-nitro-4-(((tetrahydro-2H-pyran-4-yl))benzamide (venetoclax hydroxylamine impurity, VHA). To confirm these two compounds, we have synthesized each impurity individually and analyzed it by high-performance liquid chromatography, mass spectrometry, 1 H NMR, 13 C NMR, and 2D NMR. VNO was synthesized by the oxidation of venetoclax using m-CPBA in dichloromethane to get the required N-oxide impurity. After the confirmation of the VNO impurity, the VNO impurity was heated with water at reflux in a sealed tube for 36 h to get the VHA impurity of about 6−8% after 36 h. After thorough analysis, it was confirmed that venetoclax Noxide undergoes [1,2] Meisenheimer rearrangement to form the venetoclax hydroxylamine impurity. These two impurities may be relevant reference standards in manufacturing venetoclax Active Pharmaceutical Ingredient (API) (or) tablets.