Background: South Africa has the highest burden of adolescents with perinatally-acquired HIV (APHIV) in the world. APHIV in South Africa have limited access to sexual and reproductive health (SRH) education and services specific to their HIV status. When lacking comprehensive SRH education, APHIV are prone to sexual risk behaviors that can lead to unintended pregnancy, sexually transmitted infections, and HIV transmission. The use of mHealth interventions has been shown to deliver information, foster social support, and improve decision-making skills. In this study, we evaluate how an mHealth intervention influences sexual health knowledge and behaviors in APHIV. Methods: We purposively enrolled adolescents from the intervention arm of a randomized clinical trial assessing a multi-module, moderated WhatsApp-based intervention—Interactive Transition Support for Adolescents Living with HIV (InTSHA)—within a government supported clinic in KwaMashu, an urban township of KwaZulu-Natal, South Africa. We conducted in-depth interviews based on World Health Organization guidelines for asking adolescents about SRH. We thematically analyzed data through an iterative, team-based coding approach combining deductive and inductive elements to contextualize SRH attitudes, knowledge, and behaviors before and after receiving the InTSHA intervention.Results: Of the 21 participants, 13 (61.9%) were female and the mean age was 16.6 years. Most participants reported first learning about SRH as young teenagers in school through non-targeted and negative ways, seeking clarification through peers and the internet rather than clinicians or caregivers. Participants reported that InTSHA provided a holistic and destigmatizing perspective on relationships, gender, and sexuality specific to growing up with HIV in South Africa. They praised the ability to give and receive information from peers in a moderated setting through the mHealth intervention, building their confidence, decision-making skills, and communication with partners and caregivers throughout their everyday lives. Despite reporting some technological challenges, adolescents agreed that InTSHA was convenient, confidential, and user-friendly.Conclusions: South African APHIV receive incomplete and conflicting sexual education from peers, caregivers, teachers, and technology that can be supplemented by mHealth curricula targeted for the unique needs of APHIV. Future, scaled-up mHealth interventions can destigmatize SRH by expanding access to sexual education and peer support, supplementing adolescents’ existing SRH education.