Abstract Background Schistosomiasis and fascioliasis are digenean parasitic infections and are among the neglected tropical diseases that have both medical and veterinary importance. They are found mainly in areas having limited access to safe water supply and improved sanitation. Methods A cross-sectional study was conducted to determine the prevalence of Schistosoma mansoni and Fasciola species infections and to identify associated risk factors among school children in Amhara Regional State, Ethiopia. Stool specimens were collected from 798 children (419 males, 379 females) and processed using Kato-Katz and formol-ether concentration techniques. A semi-structured questionnaire was used to collect socio-demographic and other exposure information to explore potential risk factors for the infections. Results The overall prevalence of S. mansoni and Fasciola species infections was 25.6% (95% confidence interval (CI): 22.5-28.6) and 5.5% (95% CI: 3.9-7.1), respectively. S. mansoni was present in all surveyed schools with the prevalence ranging from 12.8% (16/125; 95% CI = 5.6-20.0) to 39.7% (64/161; 95% CI = 32.2-47.2) while Fasciola species was identified in five schools with the prevalence ranging from 2.5% (4/160; 95% CI = 0.001–4.9) to 9.8% (13/133; 95% CI = 4.7–14.8). The prevalence of S. mansoni infection was significantly associated with swimming in rivers (Adjusted odds ratio (AOR): 1.79, 95% CI, 1.22–2.62; P=0.003), bathing in open freshwater bodies (AOR, 2.02; 95% CI, 1.39–2.94; P<0.001) and engaging in irrigation activities (AOR, 1.69; 95% CI, 1.19-2.39; P=0.004), and was higher in children attending Addis Mender (AOR, 2.56; 95% CI, 1.20–5.46; P=0.015 ) and Harbu schools (AOR, 3.53; 95% CI, 1.64–7.59; P=0.001). Fasciola species infection was significantly associated with consumption of raw vegetables (AOR, 2.47; 95% CI, 1.23-4.97; P=0.011) and drinking water from unimproved sources (AOR, 2.28; 95% CI, 1.11–4.70; P=0.026). Conclusion Both intestinal schistosomiasis and human fascioliasis are prevalent in the study area, affecting school children. Behaviors and access to unimproved water and sanitation are among significant risk factors. The findings are instrumental for targeted interventions.