Nitrogen (N) use in intensive agriculture can degrade groundwater resources. However, considerable time lags between groundwater recharge and extraction complicate source attribution and remedial responses. We construct a historic N mass balance of two agricultural regions of California to understand trends and drivers of past and present N loading to groundwater (1945–2005). Changes in groundwater N loading result from historic changes in three factors: the extent of agriculture (cropland area and livestock herd increased 120 and 800%, respectively), the intensity of agriculture (synthetic and manure waste effluent N input rates increased by 525 and 1500%, respectively), and the efficiency of agriculture (crop and milk production per unit of N input increased by 25 and 19%, respectively). The net consequence has been a greater-than-order-of-magnitude increase in nitrate (NO3−) loading over the time period, with 163 Gg N yr−1 now being leached to groundwater from approximately 1.3 million ha of farmland (not including alfalfa [Medicago sativa L.]). Meeting safe drinking water standards would require NO3− leaching reductions of over 70% from current levels through reductions in excess manure applications, which accounts for nearly half of all groundwater N loading, and through synthetic N management improvements. This represents a broad challenge given current economic and technical conditions of California farming if farm productivity is to be maintained. The findings illustrate the growing tension—characteristic of agricultural regions globally—between intensifying food, feed, fiber, and biofuel production and preserving clean water.