Background: Peer victimization is common among youth and associated with substance use. Yet, few studies have examined these associations longitudinally or the psychological processes whereby peer victimization leads to substance use. The current study examined whether peer victimization in early adolescence is associated with alcohol, marijuana, and tobacco use in mid- to late adolescence, as well as the role of depressive symptoms in these associations. Methods: Longitudinal data were collected between 2004 and 2011 from 4297 youth in Birmingham, Alabama; Houston, Texas; and Los Angeles County, California. Data were analyzed by using structural equation modeling. Results: The hypothesized model fit the data well (Root Mean Square Error of Approximation [RMSEA] = 0.02; Comparative Fit Index [CFI] = 0.95). More frequent experiences of peer victimization in the fifth grade were associated with greater depressive symptoms in the seventh grade (B[SE] = 0.03[0.01]; P < .001), which, in turn, were associated with a greater likelihood of alcohol use (B[SE] = 0.03[0.01]; P = .003), marijuana use (B[SE] = 0.05[0.01]; P < .001), and tobacco use (B[SE] = 0.05[0.01]; P < .001) in the tenth grade. Moreover, fifthgrade peer victimization was indirectly associated with tenth-grade substance use via the mediator of seventh-grade depressive symptoms, including alcohol use (B[SE] = 0.01[0.01]; P = .006), marijuana use (B[SE] = 0.01[0.01]; P < .001), and tobacco use (B[SE] = 0.02[0.01]; P < .001). Conclusions: Youth who experienced more frequent peer victimization in the fifth grade were more likely to use substances in the tenth grade, showing that experiences of peer victimization in early adolescence may have a lasting impact by affecting substance use behaviors during mid- to late adolescence. Interventions are needed to reduce peer victimization among youth and to support youth who have experienced victimization.