BackgroundSubstance use constitutes a major public health issue especially among adolescents as it has associated adverse behavioural, health, social and economic outcomes. However, there is a paucity of comprehensive evidence on the prevalence and associated factors of substance use (alcohol, marijuana and amphetamine) among school-going adolescents in sub-Saharan Africa (SSA). This study examined the magnitude of substance use and its associated factors among school-going adolescents in eight eligible sub-Saharan Africa countries.MethodsData for the study were obtained from the Global School-based Health Survey (2012–2017) of 8 countries in SSA (N = 16,318).ResultsFindings showed overall prevalence rates of 11.3% (95%CI = 10.8 − 11.8%), 2% (95%CI = 1.8 − 2.2%) and 2.6% (95%CI = 2.3 − 2.9%) for current alcohol use, current marijuana use and lifetime amphetamine use, respectively between 2012 and 2017. Late adolescence (15–18 years), being male, anxiety, bullying, fighting, truancy, having close friends, current cigarette smoking and tobacco use are significant risk factors for alcohol use. Anxiety, truancy, current cigarette smoking, tobacco use and suicidal attempt are significant risk factors for marijuana use. Anxiety, bullying, truancy, current cigarette smoking, tobacco use and suicidal attempt are significant risk factors for amphetamine use. Parental knowledge of activity, supervision and respect of privacy are significant protective factors of substance use.ConclusionThere is the need for comprehensive public health policies beyond school-based psycho-behavioural interventions targeting the significant risk factors of substance use among school-going adolescents in SSA.