PURPOSE: Past research has found that social, academic, and behavioral problems are linked with depression during childhood and adolescence. The present study tests a longitudinal cascade model of adolescent problems predicting depression into adulthood, while additionally testing for gender differences. METHODS: Using prospective longitudinal analysis with a sample of 808 youth followed from age 10 to 21, we tested whether social problems, school failure, and delinquency in adolescence increased risk for a major depressive episode in emerging adulthood. Structural equation modeling was used to test for gender differences. RESULTS: Both early conduct problems and adolescent school failures predisposed girls to depression in young adulthood. Among the boys, none of the problems conferred risk for depression. CONCLUSIONS: This study highlights the mutual interplay between school failure and psychological functioning. It is suggested that school adaptation in adolescence be considered a mental health issue.