The current study examined the associations between internalizing symptoms, social motivation, and gender among autistic and non-autistic youth. Caregivers of 386 participants age 6 to 14 years completed measures of their child’s internalizing symptoms and social motivation. Correlation and hierarchical regression analyses were conducted to compare internalizing symptoms and social motivation across autistic and non-autistic girls and boys. Social motivation was found to be higher among non-autistic participants compared to autistic participants, with no significant gender differences observed in social motivation within groups. Social motivation was found to be a significant predictor of internalizing symptoms. The association between social motivation and internalizing symptoms varied by gender and diagnostic status. Higher internalizing symptom scores were associated with lower social motivation among autistic girls, non-autistic girls, and non-autistic boys, but no association was found among autistic boys. The current study found that the relations between social motivation and anxiety, depression, and somatization symptoms in autistic youth varied by gender. The strong association between internalizing symptoms and social motivation among autistic girls and not autistic boys may be due to the unique social experiences and expectations associated with the intersecting gender and neurodivergent identities of autistic girls. The findings of the current study underscore the value of adopting an intersectionality perspective by considering both the influence of gender and neurodivergent identities together when addressing the social experiences and mental health of autistic youth.