Health education programmes that utilizes multicomponent classroom teaching strategies have the potential to enhance knowledge, attitudes, and actions of adolescents concerning health risk behaviors (HRBs). This study assessed the effect of a school-based context-specific health education intervention (CsHEI) on knowledge of HRBs among in-school adolescents in public- and private-owned secondary schools in Nigeria. In-school adolescents were recruited into this quasi-experimental study using stratified random sampling from secondary schools in Ile-Ife, Osun-State, Nigeria. Knowledge of HRBs was assessed pre- and post-implementation of a CsHEI. The intervention was a four-week instructor-led health education class on HRBs, delivered over a 2-h class activity per week. Data was summarized using descriptive statistics as well as Inferential statistics. With a mean age of 14.9 ± 1.56 years, a total of 145 females (54.3 %) and 122 males (45.7 %) participated in this study. Over 70 % of the participants had good knowledge of HRBs prior to the intervention with the pre-test mean general knowledge of HRB (t=-3.13, p=0.002) and knowledge of personal safety (t=-2.99, p=0.003) being significantly lower between students in public-schools compared to their private-school counterparts. Post-intervention, a significant improvement in participants' knowledge was observed in all HRB domains with over 90 % of participants having a good knowledge of HRBs. The CsHEI improved knowledge of in-school adolescents in public- and private-owned secondary schools in Osun state, Nigeria in all domains of HRBs. Integrating the CsHEI with other health behavioral change strategies can mitigate prevalence of HRBs among adolescents, thereby improving health-outcomes and well-being of adolescents.