Background Urogenital schistosomiasis is a neglected tropical disease most prevalent in sub-Saharan Africa. In the Senegal river basin, the construction of the Diama dam led to an increase and endemicity of schistosomiasis. Since 2009, praziquantel has frequently been used as preventive chemotherapy in the form of mass administration to Senegalese school-aged children without monitoring of the treatment efficacy and the prevalence after re-infection. This study aims to determine the current prevalence of urogenital schistosomiasis (caused by Schistosoma haematobium), the efficacy of praziquantel, and the re-infection rates in children from five villages with different water access. Methods The baseline prevalence of S. haematobium was determined in August 2020 in 777 children between 5 and 11 years old and a single dose of praziquantel (40 mg/kg) was administered to those positive. The efficacy of praziquantel and the re-infection rates were monitored 4 weeks and 7 months after treatment, respectively, in 226 children with a high intensity of infection at baseline. Results At the baseline, prevalence was low among children from the village of Mbane who live close to the Lac de Guiers (38%), moderate among those from the villages of Dioundou and Khodit, which neighbor the Doue river (46%), and very high at Khodit (90.6%) and Guia (91.2%) which mainly use an irrigation canal. After treatment, the observed cure rates confirmed the efficacy of praziquantel. The lowest cure rate (88.5%) was obtained in the village using the irrigation canal, while high cure rates were obtained in those using the lake (96.5%) and the river (98%). However, high egg reduction rates (between 96.7 and 99.7%) were obtained in all the villages. The re-infection was significantly higher in the village using the canal (42.5%) than in the villages accessing the Lac de Guiers (18.3%) and the Doue river (14.8%). Conclusion Praziquantel has an impact on reducing the prevalence and intensity of urogenital schistosomiasis. However, in the Senegal river basin, S. haematobium remains a real health problem for children living in the villages near the irrigation canals, despite regular treatment, while prevalence is declining from those frequenting the river and the Lac de Guiers. Trial registration ClinicalTrials.gov, NCT04635553. Registered 19 November 2020 retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04635553?cntry=SN&draw=2&rank=4