Mammalian skeletal myogenesis is a complex process that allows precise control of myogenic cells’ proliferation, differentiation, and fusion to form multinucleated, contractile, and functional muscle fibers. Typically, myogenic progenitors continue growth and division until acquiring a differentiated state, which then permanently leaves the cell cycle and enters terminal differentiation. These processes have been intensively studied using the skeletal muscle developing models in vitro and in vivo, uncovering a complex cellular intrinsic network during mammalian skeletal myogenesis containing transcription factors, translation factors, extracellular matrix, metabolites, and mechano-sensors. Examining the events and how they are knitted together will better understand skeletal myogenesis’s molecular basis. This review describes various regulatory mechanisms and recent advances in myogenic cell proliferation and differentiation during mammalian skeletal myogenesis. We focus on significant cell cycle regulators, myogenic factors, and chromatin regulators impacting the coordination of the cell proliferation versus differentiation decision, which will better clarify the complex signaling underlying skeletal myogenesis.