Adolescent girls and young women (AGYW) in sub-Saharan Africa bear a disproportionate burden of HIV. Oral pre-exposure prophylaxis (PrEP) is an effective biomedical prevention tool, but sustainable delivery models for this population are needed. School-based health clubs are a common platform for adolescent health promotion in Ghana, yet their potential for PrEP delivery is unexamined. This study assessed the feasibility and acceptability of delivering oral PrEP to AGYW through existing secondary school-based health clubs in the Ashanti Region of Ghana. We conducted a qualitative study using focus group discussions and in-depth interviews. Participants included AGYW (both health club members and non-members), school health club patrons, headteachers, parents, and local health officials. Data were analysed using thematic analysis. The concept was broadly acceptable. A key theme highlighted the value of the clubs’ peer-led structure in fostering a trusted, confidential environment for PrEP discussions. However, feasibility depended on addressing logistical and social barriers. A major concern, raised by many parents, was the potential for stigma if PrEP use was perceived to indicate sexual activity. School-based health clubs are a potentially acceptable platform for PrEP education and delivery for AGYW in this setting, primarily due to their peer-supported nature. Implementing this model would require substantial preparatory work to address stigma and operational challenges. Future programmes should integrate PrEP education within the clubs’ existing health curricula. Delivery approaches must be co-designed with students, parents, and school staff to mitigate stigma. Strong linkages to confidential, external youth-friendly health services for clinical provision are advised. Pre-exposure prophylaxis, adolescent health, HIV prevention, school health services, qualitative research, Ghana, sub-Saharan Africa. This study provides initial evidence on the potential of a school-based, peer-led model for PrEP delivery to AGYW in Ghana, identifying key acceptability factors and implementation barriers that can inform future programming.