Abstract Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with deficits in social communication and stereotypical behaviors. Whole-brain genome editing to correct single-base mutations and alleviate autistic-like behaviors in animal models has not been achieved. Here we developed an APOBEC-embedded cytosine base editor (AeCBE) system, for converting C·G to T·A base pairs. We demonstrate the effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo. We constructed a Mef2c L35P heterozygous mouse, which exhibited autistic-like behavioral deficits. We programmed AeCBE to edit the mutated C·G base pairs of Mef2cin the mouse brain, via the intravenous injection of blood brain barrier (BBB)-crossing AAV. This treatment restored MEF2C protein levels and reversed impairments in social interactions and repetitive behaviors in Mef2c mutant mice. This work presents an in vivo base editing paradigm in which a single-base mutation in the brain could be successfully corrected. One-Sentence Summary Base editing in vivo in the mouse brain corrects autistic-like behaviors.