Synaptic NMDA receptors (NMDARs) carry inward Ca2+ current responsible for postsynaptic signaling and plasticity in dendritic spines. Whether the concurrent K+ efflux through the same receptors into the synaptic cleft has a physiological role is not known. Here, we report that NMDAR-dependent K+ efflux can provide a retrograde signal in the synapse. In hippocampal CA3-CA1 synapses, the bulk of astrocytic K+ current triggered by synaptic activity reflected K+ efflux through local postsynaptic NMDARs. The local extracellular K+ rise produced by activation of postsynaptic NMDARs boosted action potential-evoked presynaptic Ca2+ transients and neurotransmitter release from Schaffer collaterals. Our findings indicate that postsynaptic NMDAR-mediated K+ efflux contributes to use-dependent synaptic facilitation, thus revealing a fundamental form of retrograde synaptic signaling. Display omitted •Postsynaptic NMDARs are the major source of synaptic K+ efflux•NMDAR-dependent K+ efflux is enhanced by coincidence of synaptic inputs•K+ elevation in the synaptic cleft enhances presynaptic Ca2+ transients•Retrograde K+ signaling is a form of computation in synaptic networks In this study, Semyanov and colleagues show that activation of postsynaptic NMDA receptors during synaptic transmission produces substantial elevation of potassium at the synapse. The potassium flows out directly through the receptors and facilitates the presynaptic release of neurotransmitter. Presynaptic facilitation depends on the amount of released potassium and, thus, on the magnitude of postsynaptic depolarization that relieves magnesium block of NMDARs and increases driving force for this ion.