BackgroundSubstance use among adolescents poses significant risks to their health, wellbeing, and development, particularly in low- and middle-income countries, including Ghana. However, little is known about the outlets and reasons for substance use among Ghanaian adolescents. This study examined the prevalence, correlates, reasons for substance use, and outlets of these substances among adolescents aged 10–17 in Ghana.MethodsData were obtained from the Department of Children, Ministry of Gender, Children, and Social Protection, Ghana, which employed a cross-sectional convergent parallel mixed-methods technique to collect quantitative and qualitative data from children aged 8–17, parents or legal guardians and officials of state institutions responsible for the promotion and protection of children’s rights and wellbeing. Overall, 4144 adolescents aged 10–17 were interviewed for the quantitative data, while 92 adolescents participated in 10 focus group discussions. Descriptive statistics, Pearson’s chi-square test, and multivariable binary logistic regression were used to analyse the quantitative data, while the qualitative data was analysed thematically.ResultsThe prevalence of substance use was 12.3%. Regarding the types of substance use, alcohol (56.9%) and cigarettes (26.4%) were the most common substances. Being a male and currently working are significant risk factors, whereas being aged 10–13, and residing in the Middle- and Northern-ecological belts of Ghana are significant protective factors of substance use. Peers, household members who use substances, drug stores, and drug peddlers are the major outlets. The reasons for substance use were fun, substance as an aphrodisiac, boosting self-confidence, dealing with anxiety, and improved social status.ConclusionsThere is a relatively high substance use among adolescents in Ghana, and this calls for a multi-sectoral approach to addressing substance use by providing risk-behaviour counselling, parental control, and effective implementation of substance use laws and regulations.