The Midwest is one of the most productive agricultural regions, but mitigating loss of nitrogen (N) from cropland is needed to improve environmental quality. Tradeoffs between crop yield and N loss have been linked largely to the inefficient use of N fertilizers, but the contributions of more systemic factors such as soil characteristics, crop sequences, and genotypes have not been thoroughly studied. This dissertation examines and quantifies the impact of various genetic, environmental and management drivers of crop yield and N-loss tradeoffs in the maize and soybean cropping systems of the US Midwest, and identifies potential management strategies to lessen these tradeoffs. To this end, a system analysis framework was employed, which used field data from small plots, long-term experiments, publicly available databases, and process-based modeling. The approach allowed for full exploration of the soil-plant-atmosphere continuum and extrapolation of the behavior of cropping systems across a wide range of weather, soil, and management. Findings from these studies indicate the prominent role of crop sequences and residue dynamics in driving tradeoffs. In maize-soybean systems, it was estimated that a majority (55%) of N losses originated from the release of native soil N into the environment due to asynchrony between soil mineralization and crop uptake. Including a rye cover crop in rotations was shown to be an effective way of improving soil N retention and reducing losses, while seldom resulting in yield tradeoffs. However, the most effective strategies also required simultaneously choosing appropriate genotypes, timely planting, and optimizing N inputs to better match crop requirements. Research also aimed to advance knowledge and modeling of various crop-soil processes including: maize, soybean and rye growth; water and N cycling; and a novel algorithm to simulate grain dry down of maize and soybean.