Objective This study examined gender differences in family, peer, partner, and mental health characteristics related to sexual experience among emotionally and behaviorally disordered students in therapeutic day schools, a population at elevated risk for negative sexual health outcomes. Methods A total of 417 13- to 20-year-old adolescents reported on their family functioning, peer and partner relationship characteristics, mental health problems, and self-reported sexual behavior. Results For boys and girls, peer influence and conduct problems predicted sexual experience, and family dysfunction was related to negative peer influence. Greater rejection sensitivity was related to less sexual experience for boys and girls. The final path model revealed indirect effects of family dysfunction on boys’ but not girls’ sexual experiences. Conclusions Findings underscore the utility of an ecological approach to understand social and personal mechanisms that increase risk and mitigate negative outcomes among emotionally and behaviorally disordered boys and girls in therapeutic day schools.