Background <p>Tobacco use among adolescents is a global epidemic; it is a major cause of morbidity and mortality in the twenty-first century. The study sought to determine the prevalence and determinants of tobacco use among in-school adolescents in Amuwo Odofin Local Government.</p> Methodology <p>A descriptive cross-sectional study among, 113 senior secondary school students from Amuwo Community Senior Secondary School and 87 junior secondary school students from Naval Town Junior Secondary School, Amuwo Odofin. The study was conducted using a multistage “sampling” technique and semi-structured self-administered questionnaire which assessed the prevalence, determinants, and barriers to quitting alcohol and perceived benefits of quitting tobacco among the students. Data was cleaned, organized, and analyzed using Epi Info 7.</p> Results <p>The mean age of respondents was 14.68 ± 1.58, while the age range of the respondents was 12–18&#xa0;years. Most of the respondents were males (69.5%). A large proportion (94.5%) of the respondents had never tried to smoke a cigarette. However, 82.5% said they would not think about smoking cigarettes in the next years. Most respondents (97.5%) had never used chewing tobacco, snuff, or dip, and about 2.0% chewed tobacco, snuff, or dip for 1 or 2&#xa0;days in the past 30&#xa0;days. Older respondents, those who spent more than N1, 000 per week, those with fathers whose level of education is primary, or mothers with a secondary level of education had a higher percentage of cigarette smoking.</p> Conclusion <p>The result showed a generally low prevalence of tobacco use among in-school adolescents in Amuwo Odofin LGA.</p>