Schistosomiasis has been deemed “the most important water-based disease from a global public-health perspective” in modern populations. To better understand the burden of schistosomiasis in ancient populations, we conducted immunologic examinations of desiccated tissue samples from two ancient Nubian populations, Wadi Halfa (N = 46) and Kulubnarti (N = 191). Saqia irrigated agriculture increases the available habitat for the aquatic vector snails and the risk of exposure. On the basis of evidence regarding the impact of saqia irrigation on schistosomiasis prevalence and transmission in modern populations, we predicted that the prevalence of Schistosoma mansoni infection would be higher in Wadi Halfa (saqia irrigation) than Kulubnarti (annual flooding). We also predicted that peak infection prevalence would occur at an earlier age within the Wadi Halfa population than the Kulubnarti population and that in both populations the prevalence of schistosomiasis would be higher in males than females due to differential water contact. The prevalence of S. mansoni was greater in the Wadi Halfa population (26.1%) than at Kulubnarti (9.4%) (P = 0.002). However, peak prevalence of infection did not occur in a younger age category within the Wadi Halfa population; prevalence of infection peaked at 66.7% in the mature adult age group (46+ years) in the Wadi Halfa population and at 16% in the later child age group (6–10 years) in the Kulubnarti population. There were no statistically significant differences in prevalence between males and females of either population. The impact of human alteration of the environment on the transmission of schistosomiasis is clearly shown in these populations. Am J Phys Anthropol, 2011. © 2011 Wiley-Liss, Inc.