Genital infection with Schistosoma haematobium is prevalent in sub-Saharan Africa. Epidemiological studies have observed that genital schistosomiasis is associated with an increased odd of HIV infection among women. We used mathematical modeling to explore the potential impact of mass preventive chemotherapy against schistosomiasis on HIV transmission in three sub-Saharan Africa countries: Angola, Kenya, and Zambia. We developed a model of female genital schistosomiasis (FGS) and HIV transmission dynamics, fitting it to data of HIV and S. haematobium prevalences as well as co-infection. We simulated targeted mass drug administration (MDA) with praziquantel to school-age children and mass treatment of the entire community. We estimated that, in S. haematobium high-risk communities, targeted annual treatment of school-age children could reduce HIV prevalence by 20% (95% CI: 12-31%) in Angola, 16% (95% CI: 10-32%) in Kenya, and 6% (95% CI: 3-18%) in Zambia after the first 20 years of intervention; and would reduce HIV incidence by 15% (95% CI: 13-32%) in Angola, 22% (95% CI: 18-42%) in Kenya, and 9% (95% CI: 3-22%) in Zambia. Extending the intervention to adults could reduce HIV prevalence by an additional 2.2% (95% CI: 0.2-12.0%) in Angola, 1.8% (95% CI: 0.1-5.2%) in Kenya, and 0.3% (95% CI: 0.1-2.1%) in Zambia; and would reduce HIV incidence by an additional 1.8% (95% CI: 0.0-14.4%) in Angola, 6.1% (95% CI: 0.5-12.6%) in Kenya, and 0.8% (95% CI: 0.0-2.7%) in Zambia. We showed that the exacerbation of HIV transmission due to FGS and the probability of developing FGS as a result of childhood infection with S. haematobium, were the most important factors in determining the effectiveness of praziquantel MDA for reducing HIV transmission. Praziquantel MDA may be an innovative measure for reducing schistosomiasis and HIV transmission in sub-Saharan Africa, the effectiveness of which varies with HIV prevalence.