The present study examined the developmental trajectories of youth depression and anxiety symptoms from 6th through 12th grade in a low-income, urban sample (N = 141; mean age = 11.75 years; 88.7% African American). The study also tested the independent contribution of parent mood disorders, anxiety disorders, and substance use disorders assessed in early childhood to initial levels and rate of change in depression and anxiety symptoms from 6th through 12th grade. Possible gender differences in symptom course and strength of parent psychopathology predictors were examined using multiple-group analysis. Results indicated that depression symptoms declined over time for males, whereas depression symptoms initially declined, but then increased for females. In contrast, male and female adolescents each showed a decline in anxiety symptoms throughout adolescence. Findings also indicated that parent mood disorders were the only predictor of youth depression and anxiety symptoms for male and female adolescents in 6th grade. Parent anxiety disorders uniquely predicted the rate of change in depression symptoms among male adolescents. These results underscore the importance of targeting parents with mood and anxiety disorders in urban families in order to reduce the risk for internalizing difficulties in their adolescent youth.