Background: The association between sedentary behavior and sexual behavior has not been investigated among adolescents, while the influential factors in this association are largely unknown. Aim: To (i) investigate the association between leisure-time sedentary behavior and sexual intercourse, and (ii) test for mediation by alcohol consumption, drug use, physical activity, bullying victimization, parental support/monitoring, loneliness, and depressive symptoms, in a large global sample of young adolescents. Methods: Data were analyzed from 34674 adolescents aged 12-15 years participating in the Global School-based Student Health Survey. Participants reported the number of hours spent in leisure-time sedentary behavior on a typical day (<1, 1-2, 3-4, 5-8, >8). Data on alcohol consumption, drug use, physical activity, bullying victimization, parental support/monitoring, loneliness, and depressive symptoms were considered as potential mediators. Outcome: Participants reported whether or not they had sexual intercourse in the past 12 months (yes/no). Results: The prevalence of past 12-month sexual intercourse was 11.9%, while the prevalence of <1, 1-2, 3-4, 5-8, and >8 hours per day of leisure-time sedentary behavior were 26.7%, 35.6%, 21.4%, 11.5%, and 4.9%, respectively. There was a dose-dependent relationship between sedentary behavior and odds of reporting sexual intercourse: compared with <1 hour/day of sedentary behavior, the OR (95%CI) of sexual intercourse associated with 1-2, 3-4, 5-8, and >8 hours/day of sedentary behavior were 1.