Using data from a randomized trial in which adolescents with depressive and substance use disorders (SUD) received treatments for both disorders in either a sequenced or coordinated manner, we (a) determine the number and nature of depression response profiles through 1-year posttreatment and (b) examine whether 8 previously identified factors predict profile membership. There were 170 adolescents (M age = 16.4 years; 22% female; 28% Hispanic, 61% Non-Hispanic White) with comorbid depressive disorder/SUD randomized to one of three sequences of receiving the Adolescent Coping With Depression Course and Functional Family Therapy for SUD (depression treatment followed by SUD treatment; SUD treatment followed by depression treatment; coordinated treatment). Depression was assessed at 7 points from baseline to 1-year follow-up. A 4-class solution fit the data best, with groups labeled Mildly Depressed Responders (57.1%), Depressed Responders (18.8%), Depressed Non-Responders (12.9%), and Depressed with Recurrence (11.2%). The 4 change profiles differed on indices of all but 1 predictor (age); most differences were driven by lower scores among Mildly Depressed Responders. Profile membership was most strongly predicted by depression severity, cognitive distortions, hopelessness, and global functioning. The strongest predictor of Nonresponse was low family cohesion, whereas Recurrence was associated with hopelessness, suicide attempts, and starting treatment near the end of the school year. Most depressed adolescents experienced a positive response that was maintained. Understanding the most common profiles of depression change during and following treatment and the variables that predict change can help improve treatment outcomes and advance tailoring efforts.