Objective: This study examined the role of academic, social, and family impairment in the pathway from externalizing psychopathology to depression among young adolescents with ADHD in a multiple mediation model. Method: The sample included adolescents with ADHD enrolled in an intervention trial. Parent ratings of externalizing psychopathology were measured at eligibility assessment, adolescent self-reported depressive symptoms were measured at eligibility and at the end of treatment, and parent-rated impairment was measured in the middle of treatment. A multiple mediation model was used to examine mediating effects of impairment types in the pathway from externalizing psychopathology to depression. Results: Parent-reported family impairment significantly mediated the association between externalizing psychopathology and depressive symptoms. Conclusions: Results suggest family impairment mediates the association between externalizing psychopathology and depressive symptoms beyond academic and social impairment for youth with ADHD. Findings implicate the importance of targeting family functioning during early adolescence to prevent depression.