A fall-planted winter cover crop is an agricultural management practice with multiple benefits that may include reducing nitrate (NO 3 ) losses from artificial drained agricultural fields. While the practice is commonly used in the southern and eastern United States, little is known about its efficacy in midwestern states where winters are longer and colder, and artificial subsurface drainage is widely used in corn-soybean systems (Zea mays L.-Glycine max L.). We used a field-tested version of the Root Zone Water Quality Model (RZWQM) to simulate the adoption of cereal rye (Secale cereale L.) as a winter cover crop and estimate its impact on NO 3 losses from drained fields at 41 sites across the Midwest from 1961 to 2005. The average annual nitrogen (N) loss reduction from adding winter rye ranged from 11.7 to 31.8 kg N ha -1 (10.4 to 28.4 lb N ac -1 ) among four simulated systems. One of the simulated treatments was winter rye overseeded (aerial seeded) into a no-till corn-soybean rotation at simulated main crop maturity (CC2). On average, this treatment reduced simulated N loss in drainage by 20.1 kg N ha -1 (17.9 lb N ac -1 ) over the sites compared to systems without winter rye (NCC2), from 47.3 to 27.2 kg N ha -1 (42.2 to 24.3 lb N ac -1 ). Adding spring tillage to this treatment and killing the rye earlier (CC3) reduced simulated N loss from 57.3 (NCC3) to 34.4 kg N ha -1 (30.7 lb N ac -1 ). Replacing the corn-soybean rotation with continuous corn and spring tillage reduced simulated N loss from 106 (NCC4) to 74.2 kg N ha -1 (CC4) (94.6 to 66.2 lb N ac -1 ). Adding a winter rye cover crop reduced N loss more in the continuous corn system despite earlier spring termination of the winter rye and slightly less N uptake by the rye possibly because of more denitrification. Regression analysis of the RZWQM variables from these sites showed that temperature and precipitation during winter rye growth, N fertilizer application rates to corn, and simulated corn yield account for greater than 95% of the simulated site-to-site variability in NO 3 loss reductions in tile flow due to winter rye. Our results suggest that on average winter rye can reduce N loss in drainage 42.5% across the Midwest. Greater N loss reductions were estimated from adding winter rye at sites with warmer temperatures and less precipitation because of more cover crop growth and more soil N available for cover crop uptake.