Groundwater nitrate contamination, especially in agriculturally active regions, is a well-recognized environmental concern. Understanding how this contamination evolves across the continental USA (CONUS) and through time is important to designing effective mitigation strategies. Despite extensive research on nitrate contamination, no existing studies can accurately predict changes in groundwater nitrate concentrations over time across the CONUS. To bridge this gap, we compiled a comprehensive dataset for a systematic evaluation of the potential influence of climate dynamics, landcover changes, and crucial soil and geological properties on groundwater contamination. We employed an interpretable machine learning approach, using 293,775 groundwater nitrate observations and 12 independent variables, to estimate annual groundwater nitrate concentrations at the county level from 2001 to 2020. Our model is the first one capable of accurately forecasting temporal changes in groundwater nitrate concentration across the entire CONUS. Our analysis reveals county level groundwater nitrate concentration changes occurred over the past two decades, particularly in regions initially with high concentrations in 2001, ranging from −16.2 mg/L-N to +6.5 mg/L-N between 2001 and 2020. 27 counties in the country appeared to have new concentrations greater than or equal to the maximum concentration level (MCL) at least once during this period. We revealed direct relationships between groundwater nitrate concentrations and climate factors, including that temperature and precipitation dominate the interannual variability in groundwater nitrate concentration in 75.2 % of counties. Notably, we have established a clear correlation between groundwater nitrate concentration and precipitation. Specifically, when annual precipitation falls below a threshold of about 748 mm, an increase of precipitation can directly result in elevated nitrate concentrations in groundwater, indicating heightened vulnerability to contamination due to climate change. This study forms a pivotal foundation for forecasting groundwater nitrate concentration changes across the continent and assessing the potential impact of climate change on future groundwater nitrate concentrations.