This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD.