Pluripotency is highly dynamic and progresses through a continuum of pluripotent stem cell states. The two states that bookend the pluripotency continuum, naïve and primed, are well characterized, but our understanding of the intermediate states and the transitions between them remain incomplete. To address this gap in knowledge, we generated comprehensive maps of the proteome, phosphoproteome, transcriptome, and epigenome of mouse embryonic stem cells transitioning from naïve to primed pluripotency. Through integrative analysis, we find that distinct waves of proteome-resetting mark pluripotent state transitions. Rapid, acute, and widespread changes to the phosphoproteome precede ordered changes to the epigenome, transcriptome, and proteome. Reconstruction of kinase-substrate networks allowed us to uncover signaling dynamics and previously unidentified substrates. Flow cytometry analysis unearthed cell surface markers that track pluripotent state transitions. Collectively, our data provide a comprehensive molecular description of the phased progression of pluripotency and a foundation for investigating mechanisms that regulate pluripotent state transitions.