Despite efforts to address HIV-infection, adolescents and young peoples’ (AYP) engagement in interventions remain suboptimal. Guided by a risk protection framework we describe factors that support positive and negative experiences of HIV and SRH interventions among AYP in rural KwaZulu-Natal, South Africa, using data from: community mapping; repeat semi-structured individual interviews (n = 58 in 2017, n = 50 in 2018, n = 37 in 2019–2020); and group discussions (n = 13). AYP who had appropriate and accurate HIV-and SRH-related information were reported to use health-care services. Responsive health-care workers, good family and peer relationships were seen to be protective through building close connections and improving self-efficacy to access care. In contrast to cross-generational relationships with men, alcohol and drug use and early pregnancy were seen to put AYP at risk. Policies and interventions are needed that promote stable and supportive relationships with caregivers and peers, positive social norms and non-judgemental behaviour within clinical services.