In Ethiopia, human schistosomiasis is caused by two species of schistosome, with the former being dominant in the country, causing infections of more than 5 million people and more than 37 million at risk of infection. What is more, new transmission foci for have been reported over the past years in the country, raising concerns over the potential impacts of environmental changes (e.g., climate change) on the disease spread. Knowledge on the distribution of schistosomiasis endemic areas and associated drivers is much needed for surveillance and control programs in the country. Here we report a study that aims to examine environmental determinants underlying the distribution and suitability of endemic areas at the national scale of Ethiopia. The study identified that, among five physical environmental factors examined, soil property, elevation, and climatic factors (e.g., precipitation and temperature) are key factors associated with the distribution of endemic areas. The model predicted that the suitable areas for schistosomiasis transmission are largely distributed in northern, central, and western parts of the country, suggesting a potentially wide distribution of endemic areas. The findings of this study are potentially instrumental to inform public health surveillance, intervention, and future research on schistosomiasis in Ethiopia. The modeling approaches employed in this study may be extended to other schistosomiasis endemic regions and to other vector-borne diseases.