Different physical, social, affective, and sexual changes take place during adolescence, such as the sexual debut. To explore the factors associated with the onset of sexual activity in adolescents attending school (12-16 years) in Bucaramanga. This analytical cross-sectional study included 440 adolescents from a public school. An instrument developed by Latin American Center for Perinatology - History of Adolescents was applied, and descriptive and bivariate analyses were conducted using a binomial regression model adjusted by age and sex, with sexual activity onset as the outcome and possible associated factors as exposures. The prevalence of the onset of sexual activity was 22.27% (95% CI: 18.56-26.46). Factors associated with greater prevalence of sexual activity onset were having a criminal record and partner PR=3.24, (95%CI: 2.60-4.05) and PR=2.00, (95%CI: 1.42-2.82), respectively. Male gender PR=1.19, (95% CI: 0.84 1.67), using tobacco PR=1.23 (95% CI: 0.73-2.06), alcohol consumption PR=1.23, (95% CI: 0.73-2.06), and other psychoactive substance use PR=1.78, (95% CI: 0.99-3.19) were risk factors; meanwhile, socializing with friends was a protective factor PR=0.27, (95% CI: 0.20-0.36). Follow-up by parents and school support decrease the risk of adolescent sexual activity onset. Furthermore, interventions in the family and school settings are important. There are conditions that could promote the beginning of sexual activity in adolescence such as being male, having a partner, having a criminal record, smoking, and consuming alcohol or other substances could promote adolescent sexual activity onset, while socializing with friends was found to be a protective factor.