Human activities have increased the flow of nitrogen (N) and phosphorus (P) over much of the Earth, leading to increased agricultural production, but also the degradation of air, soil, and water quality. Here we quantify the sources of anthropogenic N and P inputs to 76 watersheds of the St. Lawrence Basin (SLB) throughout the 20th century using NANI/NAPI (net anthropogenic N/P input to watersheds), a mass balance modeling approach, and estimate the fraction of these inputs exported to adjacent rivers. Our results show that since 1901, NANI and NAPI increased 4.5-fold and 3.8-fold, respectively, with a peak in 1991 mainly due to high atmospheric N deposition and P fertilizer application. However, the relative increase over the course of the last century was much higher in certain watersheds, particularly those where there was greater urbanization. Ranges in NANI and NAPI vary greatly among watersheds (110 to 9351 kg N km?2 yr?1 and 0.16 to 1938 kg P km?2 yr?1, respectively in 2011) and are strongly related to riverine fluxes (R2 = 0.87 and 0.71 for N and P, respectively). Our results suggest that 22% of NANI (ranging from 11% to 68% across watersheds) and 17% of NAPI (ranging from 3% to 173%) are exported to rivers. Predominant sources of inputs vary spatially and through time largely due to changes in farming practices. By tracking the main sources of inputs to specific watersheds and through time, our work provides insights for N and P management. Reduction strategies will likely need to be watershed specific, although through time, our results clearly show the large-scale impact of targeted legislation.