Thrombospondins (TSPs) are astrocyte-secreted proteins that promote central nervous system (CNS) synaptogenesis. This study shows that immature but not mature astrocytes express TSPs-1 and -2, which promote synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work with other astrocyte-derived signals to produce functional synapses. These findings identify TSPs as CNS synaptogenic proteins and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development. Astrocytes secrete two activities that affect synapse formation and function differently. TSP1 is sufficient to mimic the synapse-promoting activity of astrocyte-conditioned medium (ACM). TSP1 induces ultrastructurally normal synapses and provides evidence that synaptic structures detected by immunostaining correspond to fully developed synaptic structures observed by electron microscopy. TSP2 is a necessary component of the synapse-promoting activity of ACM. TSP2-depleted ACM reduces synapse-promoting activity to control levels, indicating that TSP2 is necessary for astrocytes to enhance synaptogenesis. TSP1 and TSP2 are expressed in the developing brain but not in the adult brain. Mice lacking both TSP1 and TSP2 form fewer synapses, indicating that these TSPs help promote normal CNS synaptogenesis in vivo. TSP-induced synapses are postsynaptically silent, lacking AMPAR responsiveness, suggesting that an unidentified astrocyte-derived signal is necessary for full postsynaptic function. TSPs are astrocyte-derived proteins that help promote CNS synaptogenesis in vitro and in vivo. The identification of TSP1 and TSP2 as CNS synaptogenic proteins has important implications for understanding normal CNS development and disease. TSP levels are dynamically regulated during development, being low in late embryonic brain, higher in postnatal brain, and low or absent in the adult brain. The downregulation of TSP1/2 levels in adult brain correlates with the relatively poor ability of the adult CNS to form new synapses. These results suggest that TSP1/2 levels act as a permissive switch that helps control the timing of CNS synaptogenesis.Thrombospondins (TSPs) are astrocyte-secreted proteins that promote central nervous system (CNS) synaptogenesis. This study shows that immature but not mature astrocytes express TSPs-1 and -2, which promote synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work with other astrocyte-derived signals to produce functional synapses. These findings identify TSPs as CNS synaptogenic proteins and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development. Astrocytes secrete two activities that affect synapse formation and function differently. TSP1 is sufficient to mimic the synapse-promoting activity of astrocyte-conditioned medium (ACM). TSP1 induces ultrastructurally normal synapses and provides evidence that synaptic structures detected by immunostaining correspond to fully developed synaptic structures observed by electron microscopy. TSP2 is a necessary component of the synapse-promoting activity of ACM. TSP2-depleted ACM reduces synapse-promoting activity to control levels, indicating that TSP2 is necessary for astrocytes to enhance synaptogenesis. TSP1 and TSP2 are expressed in the developing brain but not in the adult brain. Mice lacking both TSP1 and TSP2 form fewer synapses, indicating that these TSPs help promote normal CNS synaptogenesis in vivo. TSP-induced synapses are postsynaptically silent, lacking AMPAR responsiveness, suggesting that an unidentified astrocyte-derived signal is necessary for full postsynaptic function. TSPs are astrocyte-derived proteins that help promote CNS synaptogenesis in vitro and in vivo. The identification of TSP1 and TSP2 as CNS synaptogenic proteins has important implications for understanding normal CNS development and disease. TSP levels are dynamically regulated during development, being low in late embryonic brain, higher in postnatal brain, and low or absent in the adult brain. The downregulation of TSP1/2 levels in adult brain correlates with the relatively poor ability of the adult CNS to form new synapses. These results suggest that TSP1/2 levels act as a permissive switch that helps control the timing of CNS synaptogenesis.