Background Substance use and its relation to HIV risk among men who have sex in Africa, a population at high risk for HIV, has received little attention. Methods This systematic review summarizes and discusses findings from 68 empirical studies, published between 1980 and 2016 that included data about substance use in MSM in Africa. Results Substance use has rarely been the primary focus of studies in African MSM. In general, measurement of substance use was suboptimal. Whereas prevalence of alcohol use varied across studies, partly resulting from variety in assessment strategies, it seemed higher than in the general male population across countries. Alcohol use was associated with sexual risk practices, but not with HIV infection. The most frequently reported drug used by African MSM was cannabis. Use of other drugs, such as cocaine and heroin seemed relatively rare, although injection drug use was exceptionally high in a few studies. As alcohol, drugs were regularly used in conjunction with sex. Both alcohol and drug use were often associated with other risk factors for HIV infection, including violence and transactional sex. No interventions were found addressing substance use among African MSM. Conclusion Given high HIV-risk and prevalence in this population, substance use should be studied more in-depth, taking into account the specific social and cultural context. Assessment of substance use practices in this population has to be improved. The available information suggests, though, that there is an urgent need for interventions addressing substance use tailored to the needs of this critical population.