Based on an emerging neuroscience model of addiction, this study examines how an imbalance between two neurobehavioral systems (reward motivation and executive control) can distinguish between early adolescent progressive drug use and mere experimentation with drugs. Data from four annual assessments of a community cohort (N = 382) of 11- to 13-year-olds were analyzed to model heterogeneity in patterns of early drug use. Baseline assessments of working memory (an indicator of the functional integrity of the executive control system) and three dimensions of impulsivity (characterizing the balance between reward seeking and executive control systems) were used to predict heterogeneous latent classes of drug use trajectories from early to midadolescence. Findings revealed that an imbalance resulting from weak executive control and heightened reward seeking was predictive of early progression in drug use, while heightened reward seeking balanced by a strong control system was predictive of occasional experimentation only. Implications of these results are discussed in terms of preventive interventions that can target underlying weaknesses in executive control during younger years, and potentially enable at-risk adolescents to exercise greater self-restraint in the context of rewarding drug-related cues.