This study investigated equivalence of autism symptom domains in males and females with autism. Symptom data were obtained from 2643 children and adolescents with autism spectrum disorder (352 females, 2291 males; age range = 4–17 years) included in the Simons Simplex Collection. Items from the Social Responsiveness Scale and Autism Diagnostic Interview–Revised were mapped to nine a priori symptom dimensions. Multi-group confirmatory factor models, including measurement equivalence and item response theory analyses, examined whether males and females showed measurement or structural differences in autism symptom constructs. Results indicated mean differences in restricted interests that were not due to measurement bias. No other symptom dimension showed evidence of measurement bias and autism symptom structure was highly similar between males and females. Future studies are needed to carefully estimate any sex differences in the content, frequency, or intensity/severity of restricted interests in females and males.