Activity-dependent regulation of dendritic protein synthesis is critical for enduring changes in synaptic function, but how the unique features of distinct activity patterns are decoded by the dendritic translation machinery remains poorly understood. Here, we identify eukaryotic elongation factor-2 (eEF2), which catalyzes ribosomal translocation during protein synthesis, as a biochemical sensor in dendrites that is specifically and locally tuned to the quality of neurotransmission. We show that intrinsic action potential (AP)-mediated network activity in cultured hippocampal neurons maintains eEF2 in a relatively dephosphorylated (active) state, whereas spontaneous neurotransmitter release (i.e., miniature neurotransmission) strongly promotes the phosphorylation (and inactivation) of eEF2. The regulation of eEF2 phosphorylation is responsive to bidirectional changes in miniature neurotransmission and is controlled locally in dendrites. Finally, direct spatially controlled inhibition of eEF2 phosphorylation induces local translational activation, suggesting that eEF2 is a biochemical sensor that couples miniature synaptic events to local translational suppression in neuronal dendrites.