Adolescents in Northern Uganda are at risk of teenage pregnancies, unsafe abortions and sexually transmitted infections (STIs). There is silence on sex both at home and school. This cross sectional descriptive analytical study interviews a random sample of 827 students and 13 teachers on knowledge, perception and acceptability to a comprehensive adolescent sexual and reproductive health education in “O” and “A” level secondary schools in Gulu District. Quantitative data was analysed using SPSS 16.0. Directed content analysis of themes of transcribed qualitative data was conducted manually for common codes, sub-categories and categories. Of the 827 students; 54.3% (449) reported being in a sexual relationship especially those aged 15–17 years. Majority 96.1% (807) supported the teaching of a comprehensive ASRHE, citing no negative impact 71.5% (601). Majority 81.6% (686) agreed that such education could help prevention of STIs, abortions and teenage pregnancies, and that it should be taught by health workers 69.0% (580). Majority 76.6% (203) reported that ASRHE was not currently being taught in their schools. Students had low knowledge levels and misconceptions about ASRHE. ASRHE was highly acceptable though not being emphasized; its success in school settings requires multidisciplinary culturally sensitive approaches amongst which health workers should be frontiers.