Adolescents in sub-Saharan Africa, specifically adolescent girls and young women, young men who have sex with men, transgender persons, persons who use substances, and adolescents experiencing homelessness experience intersectional stigma, have a high incidence of HIV and are less likely to be engaged in HIV prevention and care. We conducted a thematic analysis informed by the Health and Discrimination Framework using a multiple case study design with five case studies in 3 sub-Saharan African countries. Our analysis found commonalities in adolescents’ intersectional stigma experiences across cases, despite different contexts. We characterize how intersectional stigma impacts the uptake and implementation of HIV prevention and treatment services along the continuum for adolescents. Findings reveal how intersectional stigma operates across social-ecological levels and worsens HIV-related outcomes for adolescents. We identify opportunities for implementation science research to address stigma-related barriers to the uptake and delivery of HIV services for adolescents in sub-Saharan Africa.