Background: Adolescent girls and young women (AGYW) in Eastern and Southern Africa remain disproportionately affected by HIV. Researchers have consistently demonstrated the effect of HIV-related partner communication on sexual risk behavior, such as consistent condom use and increased HIV testing. While many HIV prevention efforts primarily focus on individual-level behavior change, the role of social support networks may play a critical role in shaping AGYW’s health-related decisions. Understanding these influences is essential for promoting safer sexual practices and reducing HIV risk among AGYW. Objective: This study examined the impact of family and peer communication about sex and HIV on HIV-related partner communication among AGYW in rural South Africa. Methods: We analyzed baseline data from the HIV Prevention Trials Network (HPTN) 068, a randomized trial of a cash transfer intervention among young women aged 13 to 20 (n=688) enrolled in school in rural South Africa. Data was collected from March 2011 to December 2012. HIV-related partner communication (HPC) was defined as discussions between sexual partners about HIV prevention, testing, and condom use. Descriptive statistics and inferential statistical analyses were conducted, including Chi-Square tests and multivariable logistic regression analysis. Results: The majority of participants (83.74%) reported engaging in HPC. Significant associations were recorded between HPC and self-efficacy for condom use (p=0.001), any sex in the last 3 months (p=0.05), peer communication (p=0.001), and family communication (p=0.001). AGYW who reported discussing sex and HIV with peers (aOR=2.13, 95% CI: 1.31–3.45, p =0.002) and family (aOR=2.00, 95% CI: 1.17–3.43, p=0.011) were twice as likely to engage in HPC compared to those who did not have such discussions. Similarly, AGYW who had sex in the last 3 months had higher odds of HPC (aOR=1.95, 95% CI: 1.07-3.56, p=0.0282). Additionally, those with greater self-efficacy for condom use were significantly more likely (aOR=1.89, 95%CI: 1.19-2.99, p=0.007) to engage in HPC compared to individuals with low self-efficacy for condom use. Conclusions: These results underscore the need for HIV prevention programs to incorporate family- and peer-based strategies that enhance communication skills and empower AGYW to engage in open discussions about HIV prevention, ultimately contributing to reduced sexual risk behaviors.