Significance Embryonic stem cells and induced pluripotent stem cells have abbreviated cell cycles. To achieve this rapid proliferation, several molecular safeguards that normally distinguish healthy from transformed cells are altered. Understanding how these pluripotent stem cells balance the demands of their unique cell cycles against the need to maintain a stable genome is critical to unlocking their great promise for regenerative medicine. Here, we demonstrate that Oct4 (octamer-binding transcription factor 4), a transcription factor required to maintain pluripotency, inhibits the activation of cyclin-dependent kinase (Cdk) 1, the master regulator of mitosis, and delays mitotic entry in a nontranscriptional manner. To our knowledge, our study is the first demonstration of a nontranscriptional function of the pluripotency regulator Oct4.