Excessive substance use and obesity are underpinned by a number of shared risk factors (e.g., reward dysfunction, impulsivity). Food and drugs of abuse engage similar reward-related neural circuitry and the food–drug competition hypothesis proposes that excess consumption of food may diminish desire for drugs of abuse by competing for neural receptors associated with reward and motivation. Adolescence is a high-risk period for both increased substance use and excessive weight gain. In the present study, the authors tested whether, consistent with the food–drug competition hypothesis, elevated body mass index (BMI) across adolescence predicted fewer substance use problems in young adulthood. In a multiwave prospective study of a community sample of families enriched for high levels of substance use disorders, the authors first identified BMI trajectories across adolescence in 565 participants using latent class growth analysis. They then used maximum likelihood methods to compare the equality of mean alcohol-, drug-, and nicotine-related problems during early adulthood across adolescent BMI trajectories. Participants in the obese relative to the normal weight trajectory in adolescence had fewer drinking and illicit drug problems in early adulthood. Relative to the overweight trajectory, nicotine dependence was significantly higher among both the normal weight and obese trajectories. The current findings provide partial support for the food–drug competition hypothesis, which suggests that highly palatable foods may be rewarding enough to compete with drugs of abuse and that transdiagnostic approaches to reducing problematic substance use and overeating in adolescence may be useful. However, the relationship between nicotine and food requires further study.