Objectives. To examine the global prevalence of and factors associated with tobacco dependence among adolescents who are currently smoking. Methods. We obtained 2012 to 2019 Global Youth Tobacco Survey data on 67 406 adolescents aged 12 to 16 years from 125 countries or territories (hereafter countries). Those with tobacco dependence were defined as current smokers who felt a strong desire to smoke again within 24 hours after smoking or who had ever smoked or felt like smoking first thing in the morning. Results. The global prevalence of tobacco dependence among adolescents who were currently smoking was 38.4% (95% confidence interval [CI] = 34.0, 42.7). The prevalence was highest in high-income countries (49.8%; 95% CI = 47.0, 52.6) and lowest in lower-middle-income countries (31.2%; 95% CI = 26.9, 35.4). Secondhand smoke exposure, parental smoking, smoking among closest friends, tobacco advertisement exposure, and offers of free tobacco products were positively associated with tobacco dependence. Conclusions. Nearly 40% of adolescents who are currently smoking have tobacco dependence worldwide. Public Health Implications. Our findings emphasize the need to develop tobacco control interventions to prevent experimentation from progressing to regular smoking among adolescents who are currently smoking tobacco. (Am J Public Health. 2023;113(8):861-869. https://doi.org/10.2105/AJPH.2023.307283).