Background: Adolescent motherhood is common in South Africa and occurs against a backdrop of high HIV risk. While childbearing during adolescence may result in social and economic strain that may negatively impact health, there has been limited study of whether adolescent motherhood increases the risk of HIV or herpes simplex virus type 2 (HSV-2) acquisition or engagement in high-risk sexual partnerships. Setting: Data are from HIV Prevention Trials Network 068, a longitudinal conditional cash transfer study of adolescent girls and young women (age, 13-23) in rural South Africa. Methods: We used survival analysis to estimate hazard ratios to determine if adolescent motherhood (live birth before 20 years) predicted incident HIV and incident HSV-2 and generalized estimating equations for behavioral risk ratios to determine if adolescent motherhood was associated with transactional sex and age-disparate partnerships. Results: Of 2452 adolescent girls and young women who were HIV negative at baseline, 5% were adolescent mothers; 16% were adolescent mothers by the end of the study period. After controlling for covariates, adolescent motherhood predicted incident HSV-2 acquisition [ adjusted hazard ratios, 1.30; 95% confidence interval (CI): 1.01 to 1.95] but not HIV acquisition ( adjusted hazard ratios, 1.19; 95% CI, 0.76 to 1.86). Adolescent motherhood was also associated with being in an age-disparate partnership (adjusted risk ratio, 1.30; 95% CI: 1.07 to 1.58) but not transactional sex. Conclusion: Adolescent motherhood increased the risk of HSV-2 and engagement in age-disparate partnerships, both known risk factors for HIV infection. Sexually transmitted infection screening and/or tailored combination HIV prevention interventions that account for the context of adolescent motherhood are critical to maximize adolescent mothers' long-term health and to meet UNAIDS 95-95-95 targets by 2030.