This clinical trial is for men and women with treatment-naïve chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The results of clinical studies in previously untreated CLL have demonstrated major advances in therapy over the last decade; however, despite the impressive efficacy and safety results of single agent ibrutinib in previously untreated CLL subjects, complete responses remain low, and broader questions remain regarding the optimal duration of ibrutinib therapy. The Bcl-2 protein plays a significant role in the regulation of cell death in malignant cells. Overexpression of Bcl-2 family proteins is associated with tumor initiation, disease progression, and chemotherapy resistance. Venetoclax is a highly selective Bcl-2 family protein inhibitor that binds to Bcl-2 family proteins to potentially overcome resistance and induce cell death in cancer cells. Pre-clinical studies support combination with ibrutinib, and suggest potential enhanced activity vs each agent alone. This study has been designed to evaluate the efficacy and safety of the combination of ibrutinib and venetoclax in the treatment of previously-untreated CLL/SLL. The study will have a pre-randomization phase in which subjects will receive single-agent ibrutinib for 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles. Subsequently, subjects who achieve MRD-negative response will be randomized to receive blinded ibrutinib vs placebo. Subjects who achieve MRD-positive response will be randomized to continue the open-label combination vs continue ibrutinib only. Re-introduction of therapy is built into the study design for subjects who discontinue any of the study drugs as part of the randomization phase but may benefit from re-introduction. After discontinuing treatment, subjects will continue to be followed for survival status and subsequent anti-cancer therapy until study closure.