Background: In South Africa, many studies conducted on substance abuse among in-school youth focus on urban areas. However, anecdotal evidence suggests that rural areas are experiencing an increase in substance abuse, though there is dearth of studies in these areas.Methods: This study used a quantitative design to collect data from 629 high school learners who were in Grades 10 and 11 in public schools in rural Free State Province, to determine the prevalence of, and factors associated with substance use.Results: The sample consisted of 46% males and 54% females. Their ages ranged from 14 to 20 years, with a mean of 16.9 years. The prevalence of substance abuse was 47% (n = 295) with alcohol consumption, cigarette and dagga smoking being the most common substances used. Socio-demographically, age and gender were significantly associated with substance abuse. While behavioural variables of physical fights, serious problems with parents and friends, poor academic performance, trouble with police, having sex without condom, and having sex and regretted the next day were significantly associated with substance abuse (p = 0.05).Conclusion: The prevalence of substance abuse is very high for this rural school community, which highlights the need to pay attention to rural schools regarding substance abuse challenges.