A four-decade dataset (1974–2013) of 107,823 nitrate samples in 25,993 wells from western and eastern parts of Nebraska was used to assess long-term trends of groundwater nitrate concentration and decadal changes in the extent of groundwater nitrate-contaminated areas (NO3-N≥10 mg N/L) over the entire state. Spatial statistics and regressions were used to investigate the relationships between groundwater nitrate concentrations and several potential natural and anthropogenic factors, including soil drainage capacities, vadose zone characteristics, crop production areas, and irrigation systems. The results of this study show that there is no statistically significant trend in groundwater nitrate concentrations in western Nebraska, in contrast with the increasing trend (p \u3c .05) to the east. The spatial extent and nitrate concentrations in contaminated groundwater in center pivot-irrigated areas was less than in gravity-irrigated areas. Areas with a thicker vadose zone and larger saturated thickness of the aquifer have relatively lower nitrate concentrations. The results of a classification and regression tree (CART) model indicate the difference in the influence of physical factors on groundwater nitrate concentrations between western and eastern Nebraska, namely that groundwater nitrate concentrations correspond with vadose zone thickness, effective hydraulic conductivity, and saturated thickness in the west, while in eastern Nebraska, concentrations are correlated with average percent sand in the topsoil (0–150 cm), well depth, and effective hydraulic conductivity