IntroductionAdolescent girls and young women (AGYW) who may benefit from HIV pre‐exposure prophylaxis (PrEP) face high levels of common mental disorders (e.g. depression, anxiety). Common mental disorders can reduce PrEP adherence and increase HIV risk, yet mental health interventions have not been well‐integrated into PrEP delivery.MethodsWe conducted a four‐phase human‐centred design process, from December 2020 to April 2022, to understand mental health challenges among AGYW in Johannesburg, South Africa and barriers to integrated mental health and PrEP services. In the “Discover” phase, we conducted in‐depth interviews with AGYW and key informants (KIs) in Johannesburg. We conducted a rapid qualitative analysis, informed by the Consolidated Framework for Implementation Research (CFIR), to identify facilitators and barriers of integrated mental health and PrEP services and mapped barriers to potential implementation strategies. In the “Design” and “Build” phases, we conducted stakeholder workshops to iteratively adapt an evidence‐based mental health intervention, the Friendship Bench, and refine implementation strategies for South African PrEP delivery settings. In the “Test” phase, we piloted our adapted Friendship Bench package.ResultsInterviews with 70 Discover phase participants (48 AGYW, 22 KIs) revealed the importance of integrated mental health and PrEP services for South African AGYW. Interviewees described barriers and implementation strategies for mental health and PrEP services around the CFIR domains: intervention characteristics (e.g. challenges with AGYW “opening up”); outer Johannesburg setting (e.g. community stigma); inner clinic setting (e.g. judgemental healthcare providers); characteristics of counsellors (e.g. training gaps); and the implementation process (e.g. need for demand creation). The Design and Build workshops included 13 AGYW and 15 KIs. Implementation barriers related to the quality and accessibility of public‐sector clinic services, lay counsellor training, and community education and demand creation activities were prioritized. This led to 12 key Friendship Bench adaptations and the specification of 10 implementation strategies that were acceptable and feasible in initial pilot testing with three AGYW.ConclusionsUsing a human‐centred approach, we identified determinants and potential solutions for integrating mental health interventions within PrEP services for South African AGYW. This design process centred stakeholders’ perspectives, enabling rapid development of an adapted Friendship Bench intervention implementation package.