Groundwater is the principal source of drinking water for at least one third of Earth's human inhabitants. Thus, protection of groundwater is a critical issue in many locales. Nitrates and other contaminants that impact human health are of particular concern. Mapping of aquifer vulnerability to pollution is a critical first step in implementing groundwater management protection programs; however, mapping is often constrained by generalizations inherent in model formulation and availability of data. In this study, a groundwater vulnerability model, which employs data extracted from widely available national and statewide geospatial datasets, is used to evaluate regional groundwater pollution risk in the Elkhorn River Basin, Nebraska, USA. The model, implemented in a geographic information system (GIS), is specifically structured to address risks of nitrate contamination in agricultural landscapes; thus, land use is a key factor. Modeled groundwater vulnerability was found to be positively correlated with nitrate concentrations obtained from sampled wells. The results suggest that the approach documented here could be used effectively to model regional groundwater pollution risk in other areas.