Background. In sub-Saharan Africa, substance use among adolescents has continued to be a major public health concern, albeit poorly documented across many settings. Objective. To estimate the prevalence of substance use among adolescents in sub-Saharan Africa. Methods. We searched Pubmed, EMBASE, AJOL and Google Scholar for population-based studies on adolescents (age 10-19 years) and reporting on the prevalence of substance use across sub-Saharan Africa. Search dates were from January 2000 to December 2016. A random effects meta-analysis was conducted with pooled prevalence rates (and 95% confidence interval (95% CI)) of estimated substance abuse among adolescents in sub-Saharan Africa. Results. Twenty-seven studies across sub-Saharan Africa including 143 201 adolescents (mean age 15.6 years) were selected. The overall prevalence of ‘any substance use’ in sub-Saharan Africa was 41.6%, with the highest rate in Central Africa at 55.5%. The use of caffeine-containing products (including coffee or kola nut) was most predominant at 41.2% (95% CI 24.3-58.1) but limited to West Africa. These were followed by alcohol at 32.8% (95% CI 26.0-39.5), tobacco products 23.5% (95% CI 17.7-29.3), khat 22.0% (95% CI 12.5-31.5) and cannabis 15.9% (95% CI 12.2-19.1). Other abused substances included depressants at 11.3% (95% CI 6.5-16.1), amphetamines 9.4% (95% CI 6.0-12.9), heroin 4.0% (95% CI 3.5-4.5) and cocaine 3.9% (95% CI 1.4-6.5). Conclusion. Our study reflects a high use of psychoactive substances and drugs among adolescents in sub-Saharan Africa. It is important that interventions and rehabilitation programmes are comprehensive and targeted at adolescents and parents in these settings.