Aims: Effective sexuality and HIV/AIDS education programmes are needed to protect young people against HIV/AIDS and teenage pregnancy in Tanzania and other Sub-Saharan African countries. Using a theory- and evidence-based approach and adapting the programmes to local contexts, increases the effectiveness of these programmes. This paper describes and discusses the challenges and opportunities concerning the application of Intervention Mapping (IM) in the development and implementation of a sexuality and HIV/AIDS education programme targeting young people aged 12–14 in Tanzania. Methods: The sexuality and HIV/AIDS programme was designed in a participatory manner, involving researchers, curriculum developers and teachers’ and students’ panels. The programme comprised five lessons, organized around 23 sessions with the aim of delaying the onset of sexual intercourse and increase correct and consistent condom use among young people. The programme was delivered by trained teachers as an extracurricular lesson. Conclusions: The IM protocol facilitated the development of a comprehensive sexuality and HIV/AIDS education programme relevant and appropriate to the social cultural context and the needs of learners in Tanzania. The paper has demonstrated that, although the IM was developed in the Western context, it can be used in a flexible manner to adapt to local contexts such as those in Sub-Saharan Africa