Age-discrepant sexual relationships may place women at risk for HIV infection in South Africa. Results are based on medical records and case–control interview data of 889 sexually experienced women outpatients aged 15–29 in a Gauteng township. Women with partners at least ten years older (intergenerational) show an elevated chance of having an early sexual debut, concurrent and transactional partners, and intimate partner violence. Hardship during childhood including parental loss, food insecurity and abuse are related to age asymmetric relationships. HIV is two times more likely (aOR=1.96) with an intergenerational partner. Transactional sex increases the odds of HIV independently (aOR=1.76) as does intimate partner violence (aOR=1.6). To the extent that transactional and intergenerational sex overlap the chance of contracting HIV increases more than two-fold (uOR=4.57). Girls (15–19) with intergenerational partners face the highest chance of HIV (uOR=8.55) compared to other age groups. They are also five times more likely than controls to have lived with a cross-age partner. Our findings indicate there are multiple pathways emanating from childhood leading to women’s choice of intergenerational partners, and the link to HIV is strongest among the youngest women.