College is a critical period of transition to independence and the substantial amount of time that students have to participate in leisure activities may be conducive to substance use. However, little is known about the associations between leisure activities and substance use over time, or whether these associations differ by residential status (i.e. living with parents vs. on their own). Using latent profile analysis, this study found six distinct profiles of leisure activity participation in a racially/ethnically diverse sample of college students (N = 1207). Overall, profiles with medium levels of leisure activity participation were associated with more alcohol use, heavy drinking, and marijuana use one year later; whereas profiles with the lowest levels of leisure activity participation were associated with more cigarette use 1 year later. Identifying mechanisms through which leisure activities influence substance use can help inform prevention efforts to either reduce risks associated with participation or support protective effects.