Agriculture represents the largest source of anthropogenic nitrous oxide (N2O), a potent greenhouse gas and the dominant ozone depleting substance. Globally, the magnitude of this source is well constrained; however, large uncertainties remain at regional-scales where the development of scalable mitigation practices and policies are needed. Therefore, this thesis sought to: 1) Quantify the strength of N2O emissions linked to nitrate (NO3-) runoff and revise regional budgets accordingly; and, 2) Identify the underlying mechanisms that control terrestrial and aquatic emissions in order to help guide N2O mitigation practices. The data and analyses indicated that agricultural rivers in the U.S. Corn Belt are significant sources of N2O to the atmosphere. A large bias (9-fold) in the Intergovernmental Panel on Climate Change N2O emission accounting methodology associated with river emissions (EF5r) was identified. Using a novel gas equilibration technique, stream water N2O:NO3- ratios followed a Michaelis-Menten type relation, reaching maximum values of 4.6-times ambient saturation. This response, attributed to environmental limits on in-situ production, implies that greater NO3- concentrations will have a progressively weaker effect on N2O emissions in the Mississippi River. However, based on future NO3- runoff scenarios, these analyses project that emissions could still increase by as much as 40%. Although innovative farming techniques, such as leguminous kura clover living mulches, could curtail NO3- losses and concurrent aquatic N2O emissions, experimental evidenced based on this research showed that they stimulate soil emissions. Although soils are the largest individual source, the magnitude and importance of emission “hotspots” remains unclear. Here, field-scale N2O emissions hotspots were identified using geospatial techniques and were consistently observed in low-lying areas prone to moisture and nutrient accumulation. These analyses indicated that targeted management of hotspots could reduce emissions by as much as 17%. The findings presented here provide a roadmap for policy makers and farm managers to proactively address and mitigate agricultural N2O emissions.