Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/− ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2+/ mice, but not in Atg7CKO neuronal autophagy-deficient mice or Tsc2+/−:Atg7CKO double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR. •ASD human brain shows dendritic spine pruning defects and impaired mTOR-autophagy•mTOR overactivation causes spine pruning defects in Tsc2+/− ASD mice•Neuronal autophagy enables spine elimination with no effects on spine formation•Loss of neuronal autophagy underlies spine pruning and social interaction deficits Causes of autism are under intense investigation. Tang et al. show that humans with autism do not undergo normal synaptic pruning in childhood, due to loss of a degradation process known as autophagy. Experiments using mouse models suggest that drugs that reinstate autophagy may be beneficial.