Objectives: South Africa has one of the highest rates of sexually transmitted infections (STIs) globally, with adolescent girls and young women (AGYW) disproportionately affected due to intersecting biological, behavioral, structural, and social determinants. While HIV prevention receives sustained attention, other STIs remain under-addressed despite high prevalence and increased HIV transmission risk. This study explored STI- and vaginal infection-related knowledge, attitudes, experiences, and health-seeking behaviors among South African AGYW. Methods: A convergent parallel mixed-methods approach integrated a household survey of 4932 AGYW aged 15-24 years with 68 qualitative interviews. Descriptive quantitative analyses and qualitative thematic analysis were performed. Results: Only 16.1% (794/4932) of surveyed AGYW reported an STI diagnosis by a medical professional. Genital itching was the most common self-reported symptom (17.5%), but a further 22.5% of participants preferred not to disclose symptoms experienced in the past year. Among those reporting STI-related symptoms, most sought care from clinics/hospitals (57.1%), with older participants more likely to seek treatment. Qualitative findings revealed variation in STI knowledge, from complete unawareness to detailed understanding of transmission and symptoms, although inaccuracies persisted. Whilst school was the most common source of STI information, peers served as important information sources, albeit often inaccurate. Family members, particularly older women, were also sources of STI education, although discussions were limited by sexuality communication restrictions. Most participants had never discussed vaginal infections or STIs with anyone, illustrating communication gaps. Conclusions: In examining knowledge, attitudes, experiences and health seeking behaviors of South African AGYW in relation to vaginal infections and STIs, our study found that persistent shame, stigma, and embarrassment act as key barriers to enacting preventative and health-seeking behaviors that could treat and prevent further infections. Findings underscore the need for comprehensive, accurate STI and vaginal health education and service provision for AGYW that addresses misconceptions, stigma and shame.