Background: The Undetectable = Untransmittable (U=U) message that people with HIV who maintain an undetectable viral load on antiretroviral therapy cannot sexually transmit the virus is scientifically established, yet awareness among South African adolescents remains poorly understood. This study assessed teenagers’ knowledge, perceptions, and acceptance of U=U in Mossel Bay Municipality, Western Cape. Methods: A qualitative, descriptive-exploratory study using semi-structured interviews with 15 purposively sampled teenagers (aged 13–19) across six schools. Interviews were transcribed and thematically analysed in ATLAS.ti, with a second reviewer coding a subset of transcripts. Results: Basic HIV knowledge was consistently accurate, but U=U awareness was low; 60% (9/15) had never heard the term, and understanding among the rest was partial. Only 46.7% (7/15) had tested HIV, citing fear, procedural anxiety, and parental gatekeeping as barriers; testing-related stigma persisted even among those who tested negatively. Once introduced to U=U, participants responded with cautious hope, distinguishing between acceptance in friendships versus more conditional acceptance in romantic relationships. Stigma, endorsed by all participants, was the dominant barrier, compounded by traditional, religious, and family silence. Conclusions: Teenagers possess the capacity to understand U=U; once explained, no downsides were identified. The core challenge is reach and trust, not receptiveness. Curriculum integration, provider training, and peer-led messaging are recommended.