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Age-disparate sexual relationships with older men may drive high rates of HIV acquisition in young women in sub-Saharan Africa, but evidence is limited. We investigate the association between age-disparate relationships and HIV incidence in Manicaland, Zimbabwe.A general-population open-cohort study (six surveys) (1998–2013).A total of 3746 young women aged 15–24 years participated in consecutive surveys and were HIV-negative at the beginning of intersurvey periods. Last sexual partner age difference and age-disparate relationships [intergenerational (≥10 years age difference) and intragenerational (5–9 years) versus age-homogeneous (0–4 years)] were tested for associations with HIV incidence in Cox regressions. A proximate determinants framework was used to explore factors possibly explaining variations in the contribution of age-disparate relationships to HIV incidence between populations and over time.About 126 HIV infections occurred over 8777 person-years (1.43 per 100 person-years; 95% confidence interval = 1.17–1.68). Sixty-five percent of women reported partner age differences of at least 5 years. Increasing partner age differences were associated with higher HIV incidence [adjusted hazard ratio (aHR) = 1.05 (1.01–1.09)]. Intergenerational relationships tended to increase HIV incidence [aHR = 1.78 (0.96–3.29)] but not intragenerational relationships [aHR = 0.91 (0.47–1.76)]. Secondary education was associated with reductions in intergenerational relationships [adjusted odds ratio (aOR) = 0.49 (0.36–0.68)]. Intergenerational relationships were associated with partners having concurrent relationships [aOR = 2.59 (1.81–3.70)], which tended to increase HIV incidence [aHR = 1.74 (0.96–3.17)]. Associations between age disparity and HIV incidence did not change over time.Sexual relationships with older men expose young women to increased risk of HIV acquisition in Manicaland, which did not change over time, even with introduction of antiretroviral therapy.