Objective To identify risk factors for HIV infection among young women aged 15-24 years reporting one lifetime partner in South Africa. Design In 2003, we conducted a nationally representative household survey of sexual behaviour and HIV testing among 11 904 young people aged 15-24 years in South Africa. This analysis focuses on the subset of sexually experienced young women with only one reported lifetime sex partner (n = 1708). Methods Using the proximate determinants framework and the published literature we identified factors associated with HIV in young women. The associations between these factors and HIV infection were explored in multivariable logistic regression models. Results Of the young women, 15% reporting one lifetime partner were HIV positive. In multivariable analyses, young women who had not completed high school were more likely to be infected with HIV compared with those that had completed high school (AOR 3.75; 95% CI 1.34-10.46). Conclusions Young South African women in this population were at high risk of HIV infection despite reporting only having one lifetime partner. Few individual level factors were associated with HIV infection, emphasizing the importance of developing HIV prevention interventions that address structural and partner level risk factors.