OBJECTIVE: To investigate the effect of exposure to MTV Shuga:Down South' (MTVShuga-DS) during the scale-up of combination HIV-prevention interventions on awareness and uptake of sexual reproductive health (SRH) and HIV-prevention services by adolescent girls and young women (AGYW). DESIGN: One longitudinal and three cross-sectional surveys of representative samples of AGYW. SETTING: AGYW in four South African districts with high HIV prevalence (>10%) (May 2017 and September 2019). PARTICIPANTS: 6311 AGYW aged 12-24. MEASURES: Using logistic regression, we measured the relationship between exposure to MTV Shuga-DS and awareness of pre-exposure prophylaxis (PrEP), condom use at last sex, uptake of HIV-testing or contraception, and incident pregnancy or herpes simplex virus 2 (HSV-2) infection. RESULTS: Within the rural cohort 2184 (85.5%) of eligible sampled individuals were enrolled, of whom 92.6% had at least one follow-up visit; the urban cross-sectional surveys enrolled 4127 (22.6%) of eligible sampled individuals. Self-report of watching at least one MTV Shuga-DS episode was 14.1% (cohort) and 35.8% (cross-section), while storyline recall was 5.5% (cohort) and 6.7% (cross-section). In the cohort, after adjustment (for HIV-prevention intervention-exposure, age, education, socioeconomic status), MTVShuga-DS exposure was associated with increased PrEP awareness (adjusted OR (aOR) 2.06, 95% CI 1.57 to 2.70), contraception uptake (aOR 2.08, 95% CI 1.45 to 2.98) and consistent condom use (aOR 1.84, 95% CI 1.24 to 2.93), but not with HIV testing (aOR 1.02, 95% CI 0.77 to 1.21) or acquiring HSV-2 (aOR 0.92, 95% CI 0.61 to 1.38). In the cross-sections, MTVShuga-DS was associated with greater PrEP awareness (aOR 1.7, 95% CI 1.20 to 2.43), but no other outcome. CONCLUSIONS: Among both urban and rural AGYW in South Africa, MTVShuga-DS exposure was associated with increased PrEP awareness and improved demand for some HIV prevention and SRH technologies but not sexual health outcomes. However, exposure to MTVShuga-DS was low. Given these positive indications, supportive programming may be required to raise exposure and allow future evaluation of edu-drama impact in this setting.