ABSTRACT Considerable heterogeneity exists in adolescent substance use development. To most effectively prevent use, distinct trajectories of use must be identified as well as differential associations with predictors of use, such as leisure experience. The current study used a person‐centered approach to identify distinct substance use trajectories and how leisure is associated with trajectory classes. Data came from a larger efficacy trial of 2.249 South African high school students who reported substance use at any time across 8 waves. Growth mixture modeling was used to identify developmental trajectories of substance use and the influence of healthy leisure. Results identified three increasing and one stable substance use trajectory and subjective healthy leisure served to protect against use. This study is the first of its kind to focus on a sample of South African adolescents and serves to develop a richer understanding of substance use development and the role of healthy leisure. , Highlights Four distinct substance use trajectories included one stable and three increasing. Subjective healthy leisure was associated with low/rare use trajectory. Leisure planning efficacy was associated with extreme use trajectories.