Developmental neuroscience models suggest that changes in responsiveness to incentives contribute to increases in adolescent risk behavior, including substance use. Trajectories of sensitivity to reward (SR) and sensitivity to punishment (SP) were examined and tested as predictors of escalation of early substance use in a community sample of adolescents (N = 765, mean baseline age 11.8 years, 54% female). SR and SP were assessed using a laboratory task. Across three annual assessments, SR increased, and rapid escalation was associated with increases in substance use. SP declined and was unrelated to substance use. Findings support contemporary views of adolescent brain development and suggest that early adolescent substance use is motivated by approach responses to reward, rather than failure to avoid potential aversive consequences.