Objective: Innovative public health approaches are required to improve human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) education and prevention among adolescents, one of the most vulnerable groups to HIV/AIDS. Consequently, elearning and classroom instruction was assessed for HIV/AIDS knowledge uptake and internalizing among South African and Irish pupils between the ages of 11 and 16 years. Method: An HIV/AIDS intervention was implemented based on a quasi-experimental design using experimental and control groups. Experimental group pupils underwent an elearning programme and the control group used the same material in workbooks in a classroom setting. The McNemar test assessed change in both groups' knowledge levels from baseline to post-intervention. A theoretical framework guided by the conflict theory and health belief model strengthened the learning material. Discussions took place in the classroom and in an eforum; the latter was qualitatively analysed using thematic content analysis. Results: A significant increase (P < 0.01) in HIV/AIDS knowledge uptake was experienced by the experimental group compared to a decline of 1.6% in the control group from baseline to post-intervention. Internalization of HIV/AIDS knowledge emerged in the eforum among experimental group pupils, while the classroom discussions faced structural barriers. Learning outcomes were demonstrated by higher marks achieved in the experimental than control group brochures, the outcome of the learning process. Conclusion: Elearning proved a superior technique to classroom instruction for HIV/AIDS knowledge uptake and internalizing and should be considered for wider implementation.