Groundwater nitrate (NO3-) and sulfate (SO42-) pollution in semi-arid regions has attracted widespread attention. However, unveiling the dynamics and sources of NO3-and SO42-in regional groundwater is challenging because of complex anthropogenic activities and hydrogeological conditions. This study combined physicochemistry and multiple stable isotopes (52H-H2O, 518O-H2O, 515N-NO3-, 518O-NO3-, 534S-SO42-, and 518O-SO42-) to explore the spatiotemporal patterns, driving factors, sources, and potential health hazards of NO3-and SO42-in groundwater on the Loess Plateau, China. Results showed that NO3-and SO42-concentrations exhibited significant spatiotemporal variations between the wet and dry seasons. The primary factors controlling the NO3-spatial difference were NDVI, land use type, and distance to mining area and precipitation, distance to mining area, and NDVI in the wet and dry seasons, respectively. Distance to river, precipitation, and evaporation in the wet season and NDVI, precipitation, and elevation in the dry season were the dominant drivers of spatial heterogeneity in SO42-. The explanatory power of the interaction between the two factors was greater than that of any individual factor. Soil organic nitrogen, ammonium fertilizer, and manure and sewage attributed to agricultural activities contributed the most to NO3-in groundwater. Sulfide oxidation and evaporite dissolution were the most prominent SO42-sources. Denitrification and sulfate reduction were prevalent in the wet season, while nitrification was dominant in the dry season. Health risk assessment suggested that children faced higher non-carcinogenic risks than adults in both wet and dry seasons. This study provides valuable insights into regional scale groundwater pollution in semi-arid regions.