This study aimed to investigate the impact of sex education on knowledge levels and mitigating spread of STDs among students in Highland Secondary School, located in Kisaasi, Uganda. Sexual health issues continue to affect adolescents' well-being and compromise their potential. While sexuality is a sensitive topic, education can empower young people to make informed choices. A mixed research design was used incorporating quantitative and qualitative approaches. The target population was all students in senior one to senior four classes, totaling to 800 learners. Stratified random sampling was employed to select a sample of 200 students proportionately distributed across gender and classes to participate in the study. Primary data collection involved administering semi-structured questionnaires to the 200 sampled students to collect quantitative data on their sex knowledge, attitudes and risk behaviors. This was complemented by in-depth interviews conducted with 20 teachers and guidance counsellors to obtain qualitative perspectives on the school's sex education approach, impact and existing challenges. Documentary review also provided information from students' medical records on reported STD cases over the last five years. Data collected was analyzed using both descriptive and inferential statistics. Key findings showed students who underwent sex education lessons had significantly higher levels of awareness about reproductive health issues like prevention of infections, contraceptive use and responsible sexual relations compared to their counterparts without such exposure. These learners also displayed more favorable attitudes towards abstinence and demonstrated less risky behaviors that predisposed them to STDs. Notably, the school had registered declines in reported STD incidence rates among students from 15% in 2015 to the current 7% following the introduction of more enhanced sex education components. Results of the study clearly validate the important role sex education plays in equipping adolescents with vital life skills that promote sexual health and well-being.