The medial prefrontal cortex (mPFC) and the right temporo-parietal junction (rTPj) are highly involved in social understanding, a core area of impairment in autism spectrum disorder (ASD). We used fMRI to investigate sex differences in the neural correlates of social understanding in 27 high-functioning adults with ASD and 23 matched controls. There were no differences in neural activity in the mPFC or rTPj between groups during social processing. Whole brain analysis revealed decreased activity in the posterior superior temporal sulcus in males with ASD compared to control males while processing social information. This pattern was not observed in the female sub-sample. The current study indicates that sex mediates the neurobiology of ASD, particularly with respect to processing social information.