Information about microbial water quality is critical for managing water safety and protecting public health. In low-income countries, monitoring all drinking water supplies is impractical because financial resources and capacity are insufficient. Data sets derived from satellite imagery, census, and hydrological models provide an opportunity to examine relationships between a suite of environmental risk factors and microbial water quality over large geographical scales. We investigated the relationships between groundwater fecal contamination and different environmental parameters in Uganda and Bangladesh. In Uganda, groundwater contamination was associated with high population density (p < 0.001; OR = 1.27), high cropland coverage (p < 0.001; OR = 1.47), high average monthly precipitation (p < 0.001; OR = 1.14), and high surface runoff (p < 0.001; OR = 1.37), while low groundwater contamination was more likely in areas further from cities (p < 0.001; OR = 0.66) and with higher forest coverage (p < 0.001; OR = 0.70). In Bangladesh, contamination was associated with higher weekly precipitation (p < 0.001; OR = 1.44) and higher livestock density (p = 0.05; OR = 1.11), while low contamination was associated with low forest coverage (p < 0.001; OR = 1.23) and high cropland coverage (p < 0.001; OR = 0.80). We developed a groundwater contamination index for each country to help decision-makers identify areas where groundwater is most prone to fecal contamination and prioritize monitoring activities. Our approach demonstrates how to harness satellite-derived data to guide water safety management.