BACKGROUND Adolescent substance use is a global concern. Identifying factors associated with it can help in preparing prevention programmes. OBJECTIVE The objectives were to determine the sociodemographic factors associated with substance use and the prevalence of associated psychiatric morbidity among secondary school students in Ilorin. METHODS Instruments used were a sociodemographic questionnaire, a modified WHO Students' Drug Use Survey Questionnaire, and the General Health Questionnaire-12 (GHQ-12) which was used to determine psychiatric morbidity, using a cut-off score of 3. RESULTS Substance use was associated with older age groups, male gender, parental substance use and poor relationship with parents, and urban location of school. Reported religiosity did not confer protection against substance use. The overall prevalence of psychiatric morbidity was 22.1% (n= 442). Psychiatric morbidity was more common among users of opioids, organic solvents, cocaine and hallucinogens, with current opioid users having ten times the odds of psychiatric morbidity. CONCLUSIONS Factors influencing adolescent substance use serve as a substrate for interventions. A good relationship with parents and teachers are protective factors, while parental substance use calls for holistic psychosocial support. The association of substance use with psychiatric morbidity highlights the need to incorporate behavioural treatment in substance use interventions.