Objectives: To estimate individual and group trajectories of substance use among heterosexual and sexual minority adolescent females (SMFs) and evaluate longitudinal substance use disparities. Methods: Annual self-reported substance use data (frequency of cigarette, alcohol, and marijuana use) across ages 13-20 years were used to estimate individual and group trajectories using the Pittsburgh Girls Study--a large population-based study of urban-living adolescents. Participants were 2263 females (ages 13-16 years at baseline of current analysis) who were 60% racial/ethnic minority, and 17% sexual minority (lesbian or bisexual). Multilevel models compared SMF versus heterosexual differences in substance use over time controlling for race, single parent status, public assistance status, and caregivers' low education status. Results: SMFs reported higher frequencies of cigarette, alcohol, and marijuana use across the entire age continuum. SMFs demonstrated more rapid escalations in substance use during early adolescence resulting in larger substance use disparities by the time they reached emerging adulthood. Conclusions: Early adolescence is a critical period of risk for increases in substance use among SMFs. Early intervention and prevention efforts may help reduce the rapid escalation in substance use and decrease substance use disparities over time.