Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile [postnatal day 9 (P9), P15, P21, P27], adolescent (P35) and different adult ages (P70, P140, P280) of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time. Proteins of the presynaptic active-zone and postsynaptic element showed increased levels over time; proteins involved in protein synthesis or neurite outgrowth generally decreased in abundance. In several cases, proteins from a single functional molecular entity, e.g., subunits of the NMDA receptor, showed profound differences in their temporal regulation, which may reflect specific synaptic development features of connectivity, strength and plasticity.