The anti-apoptotic protein BCL-2 plays critical roles in regulating lymphocyte development, immune responses, and has also been implicated in tumorigenesis and tumor survival. However, it is unknown whether BCL-2 is critical for anti-tumor immune responses. We evaluated whether venetoclax, a selective small-molecule inhibitor of BCL-2, would influence the anti-tumor activity of immune checkpoint inhibitors (ICIs). We demonstrate in mouse syngeneic tumor models that venetoclax can augment the anti-tumor efficacy of ICIs accompanied by the increase of PD-1+ T effector memory cells. Venetoclax did not impair human T cell function in response to antigen stimuli in vitro and did not antagonize T cell activation induced by anti-PD-1. Further, we demonstrate that the anti-apoptotic family member BCL-XL provides a survival advantage in effector T cells following inhibition of BCL-2. Taken together, these data provide evidence that venetoclax should be further explored in combination with ICIs for cancer therapy.