INTRODUCTION: Adolescent substance use has a number of adverse consequences for both the individual and society. Anecdotal evidence suggested the existence of a serious substance use problem among learners in Atteridgeville, part of the City of Tshwane Metropolitan Municipality in Gauteng, South Africa. OBJECTIVES: The objectives of the study were to determine the prevalence rates and age of initiation of substance use among learners attending secondary schools in Atteridgeville, and the factors, if any, associated with cannabis use. METHODS: This was a cross-sectional study. A cluster sampling technique was employed. Twenty-two of the total of 191 grade 8 - 11 classes in the nine Atteridgeville secondary schools were randomly selected, with all 895 learners in the selected classes being invited to participate. Self-administered questionnaires were used to collect data. Statistical analysis was conducted using the survey estimation commands in STATA 10.0. RESULTS: The lifetime prevalence rates for the three most commonly used substances were 51.4% (95% confidence interval (CI) 41.5 - 61.5%) for alcohol, 25.2% (95% CI 17.1 - 33.3%) for cigarettes and 13.2% (95% CI 8.3 - 18.2%) for cannabis. Alcohol was also found to have the lowest mean age of initiation at 14.6 years (standard deviation 2.0). Based on CRAFFT screening scores, 30.3% (95% CI 24.5 - 36.1%) of learners met the criteria for possible problem substance use. Following multivariate analysis, the factors found to be significantly associated with lifetime cannabis use were age, gender, lifetime cigarette use, lifetime alcohol use, the number of illicit drug users among the learners' five closest friends, and an older sibling with a history of illicit drug use. CONCLUSION: The results of the study suggest that substance use among learners in Atteridgeville is widespread and that a comprehensive intervention strategy is required.