Sex workers have long been considered a high-risk group for HIV infection, but to date little quantitative research has explored the association between HIV risk and exchange of sex for material gain by women in the general population. The objective of this study was to estimate the prevalence of such transactional sex among women attending antenatal clinics in Soweto, South Africa, to identify demographic and social variables associated with reporting transactional sex, and to determine the association between transactional sex and HIV serostatus. We conducted a cross-sectional study of women seeking antenatal care in four Soweto health centres who accepted routine antenatal HIV testing. Private face-to-face interviews covered socio-demographics, sexual history and experience of gender-based violence. 21.1% of participants reported having ever had sex with a non-primary male partner in exchange for material goods or money. Women who reported past experience of violence by male intimate partners, problematic substance use, urban residence, ever earning money, or living in substandard housing were more likely to report transactional sex, while women who reported delayed first coitus, were married, or had a post-secondary education were less likely to report transactional sex. Transactional sex was associated with HIV seropositivity after controlling for lifetime number of male sex partners and length of time a woman had been sexually active (OR = 1.54, 95% CI: 1.07, 2.21). Women who reported non-primary partners without transactional sex did not have increased odds of being HIV seropositive (OR = 1.04, 95% CI: 0.75, 1.43). We conclude that transactional sex may place women at increased risk for HIV, and is associated with gender-based violence, substance use and socio-economic disadvantage. Research, policy and programmatic initiatives should consider the role of transactional sex in women's HIV risk, with attention to the intersecting roles of violence, poverty, and substance use in shaping women's sexual behaviour.