Abstract Background and purpose Previous studies have revealed abnormal regional homogeneity (ReHo) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the association between ReHo aberrance and clinical symptoms in individuals with ASD. Methods Forty‐eight adolescents with high‐functioning ASD and 63 group‐matched typically developing (TD) controls received functional magnetic resonance imaging at rest. Group‐level analysis was performed to detect differences in ReHo between ASD and TD. Evaluation of symptom severity in individuals with ASD was based on the Autism Behavior Checklist (ABC). Voxel‐wise correlation analysis was undergone to examine the correlations between the symptom severity and ReHo map in individuals with ASD within brain areas with ReHo abnormalities. Results Compared with the TD controls, individuals with ASD exhibited increased ReHo in the bilateral anterior cingulate cortex, left caudate, right posterior cerebellum (cerebellar tonsil), and bilateral brainstem and decreased ReHo in the left precentral gyrus, left inferior parietal lobule, bilateral postcentral gyrus, and right anterior cerebellum (culmen). The correlation analysis indicated that the ReHo value in the brainstem was negatively associated with the ABC total scores and the scores of Relating factor, respectively. Conclusions Our findings indicated that widespread ReHo abnormalities occurred in ASD, shedding light on the underlying neurobiology of pathogenesis and symptomatology of ASD.