Background Schistosoma is one of the prevalent parasitic infection in humans and animals. Schistosomiasis in children is particularly serious and results in liver and spleen enlargement, anemia, stunting, reduced ability to learn and death. The aim of this study was to measure the prevalence and distribution of schistosomiasis in children, rodents and snail populations in Aleffa and Takusa districts, north-west Ethiopia. Methods Disease status and exposure were simultaneously measured from December 2020 to December 2021. School children's stool specimens were collected for schistosomiasis examination by Kato Katz and formal-ether techniques. Live rodents and snails were trapped and collected in search of adult schistosoma, eggs, and cercariae, respectively. Multiple logistic regression analytic technique by using SPSS version 20 was conducted. Results Of 460 stool specimens examined, 116 (25.22) were found positive for S. mansoni infection. In the present finding, the possible determinants for the occurrence of intestinal schistosomiasis in school children were female sex (AOR = 1.09, 95% CI: 1.37–2.96); working with bare foot (AOR = 1.21, 95% CI: 1.08–1.52); skin cut/abrasion history (AOR = 3.6, 95% CI: 1.08–7.43) and swimming habit (AOR = 1.58, 95% CI: 1.33–1.99). The overall (n = 108) rodent prevalence of S. mansoni was 23 (21.3%). Only 6 snails were shedding the infective stage of schistosoma cercariae. Conclusion The study revealed that there is a moderate prevalence of schistosomiasis in different hosts. Thus, multi-host intervention is crucial to achieving the goal of interrupting transmission of schistosomiasis in the study area. Further research to better understand and exploit the broader environmental, ecological context and encompassing dynamic interactions between all hosts over time will be crucial for building predictive models beyond the known fact of having or not having reservoirs/hybridization of schistosoma in our study area.