There are few studies on the predictors of long-term course of major depressive disorder (MDD) with an onset in childhood and adolescence. Studies have relied on variable-centered methods, utilizing psychosocial and clinical characteristics to predict depression outcomes. However, fewer studies have used person-centered approaches that rely on profiles of functioning to predict course and outcomes of depression. This study examined the long-term course and outcome of early onset depression as a function of profiles of psychosocial and clinical characteristics in adolescence. Participants from the Oregon Adolescent Depression Project with a history of MDD by study entry (Mage = 16.29 years) and who had follow-up assessments at age 30 were included (n = 215). Psychosocial and clinical constructs, including domains of internalizing problems, externalizing problems, correlates of internalizing problems, adolescent stress, and social support, were assessed in adolescence. Latent profile analyses found a 3-class solution with Low Negative Cognitive Style (LNCS; 27.9%); Internalizing and High Negative Cognitive Style (INT/HNCS; 53.9%); and Internalizing and High Negative Cognitive Style plus Poor Interpersonal Functioning and High Stress (INT/HNCS+ ; 18.1%). Overall, classes differed in depression morbidity, such that the INT/HNCS+ class had the greatest depression morbidity across follow-up assessments. Social adjustment differed between all classes, with the INT/HNCS+ class showing the worst functioning, the LNCS class showing the best functioning, and the INT/HNCS class falling in the middle. Patterns of clinical and psychosocial functioning were differentially associated with long-term depression and social adjustment among youth with depression.