Substance use trajectories were examined from early adolescence to young adulthood among a diverse sample of 998 youths. Analysis of longitudinal data from ages 12 to 24 identified distinct trajectories for alcohol, marijuana, and tobacco use. Modeling revealed 8 alcohol, 7 marijuana, and 6 tobacco use trajectories. Analyses assessed risk for substance use problems in early adulthood within each trajectory, as well as overlap among alcohol, marijuana, and tobacco use trajectories. Findings confirmed that adolescents with early- and rapid-onset trajectories are particularly vulnerable to the development of problematic substance use in early adulthood. However, analyses also identified an escalating high school onset trajectory for alcohol and for marijuana use that was equally prognostic of problem use in adulthood. Moreover, tobacco use in early adolescence was associated with developing high-risk marijuana and alcohol use patterns. Random assignment to the Family Check-Up intervention was found to reduce risk for membership in the high-risk marijuana use trajectories, suggesting that family-based approaches delivered during adolescence can prevent escalations to problematic substance use. These findings suggest the importance of developmental heterogeneity and equifinality in considering prevention for alcohol and drug use.