“We recently uncovered a signaling mechanism by which the endocannabinoid anandamide mediates the action of oxytocin, a neuropeptide that is crucial for social behavior, to control social reward. Oxytocin signaling has been implicated in autism spectrum disorder (ASD), and social reward is a key aspect of social functioning that is thought to be disrupted in ASD. Therefore, as a proof of principle for the core component of ASD—social impairment—we tested an endocannabinoid-enhancing compound on two widely studied mouse models of ASD, the BTBR and fmr1^−/− (model of Fragile X Syndrome). Remarkably, we found that FAAH blockade completely reversed the social impairment in both mouse models. CB₁ receptor blockade prevented the prosocial action of FAAH inhibition in BTBR mice. The results suggest that increasing anandamide activity at CB₁ receptors improves ASD-related social impairment and identify FAAH as a novel therapeutic target for ASD.