Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition, affecting cognition and behavior throughout the life span. With recent advances in neuroimaging techniques and analytical approaches, a considerable effort has been directed toward identifying the neuroanatomical underpinnings of ASD. While gray-matter abnormalities have been found throughout cortical, subcortical, and cerebellar regions of affected individuals, there is currently little consistency across findings, partly due to small sample-sizes and great heterogeneity among participants in previous studies. Here, we report voxel-based morphometry of structural magnetic resonance images in a relatively large sample of high-functioning adults with ASD (n = 66) and matched typically-developing controls (n = 66) drawn from multiple studies. We found decreased gray-matter volume in posterior brain regions, including the posterior hippocampus and cuneus, as well as increased gray-matter volume in frontal brain regions, including the medial prefrontal cortex, superior and inferior frontal gyri, and middle temporal gyrus in individuals with ASD. We discuss our results in relation to findings obtained in previous studies, as well as their potential clinical implications.