Background: Substance use and substance use disorders are increasingly becoming a global public health problem and in sub-Saharan Africa, the prevalence among the youths has been increasing at an alarming rate. However, limited published data regarding this subject is available in sub-Saharan Africa. This systematic review therefore, aimed to assess the prevalence of substance use/ substance disorders and associated factors among the youths in sub-Saharan Africa. Methods: This systematic review was conducted in line with the PRISMA guidelines. We searched PubMed, Google Scholar, the Cochrane Library, African Journals Online (AJOL), EMBASE and Science Direct database. Additional search included review of references in articles and search of the gray literature. The search was conducted on November 12, 2023 and included only studies that were published in English language between 2010 and 2022. Results: A total of 18 studies were selected. The overall prevalence of substance use disorders among the youths in sub-Saharan Africa was 67.9% (95%CI [48.2%-85.1%]) with the highest prevalence of 80% reported in Malawi, whereas the overall prevalence of substance use disorders was 19.1% [95% CI (16.7%-36.4%)] with the highest prevalence of 34.8% reported in Ethiopia. In this review, alcohol and cigarette smoking were the most prevalent substances used among the youths in sub-Saharan Africa, followed by cannabis and khat. In this systemic review, male gender, increasing age, living in urban areas, availability of substances , family history of substance use, having friends who use substances, lack social support, lack parental of supervision , having had engaged in sexual intercourse, being bullied, ever involved in a physical fight ,alcohol consumption, cigarette smoking and feeling insecure within the family were factors significantly associated with substance use/ substance use disorders among the youths in sub-Saharan Africa. Conclusion: Findings from this systematic revie