Existing work has identified perceived discrimination as a risk factor that may contribute to the relatively poorer academic outcomes exhibited by Mexican-origin adolescents in the U.S. The current study examined the longitudinal associations among perceived discrimination and three indices of adolescent adjustment in the school setting (i.e., grade point average, teacher reports of externalizing, adolescents' deviant peer associations) among 178 Mexican-origin adolescents (53% female). Ethnic identity affirmation was examined as a protective factor expected to reduce the negative effects of discrimination on adolescents' adjustment, and gender was examined as a potential moderator of the associations of interest. Findings indicated that the deleterious effects of discrimination on adolescents' adjustment in school were particularly salient for Mexican-origin male adolescents. Importantly, ethnic identity affirmation emerged as a protective factor for Mexican-origin male adolescents by buffering the negative effects of discrimination on their externalizing behaviors in school. (Contains 3 tables and 3 figures.)