Cover crops can reduce nitrogen (N) loss to subsurface drainage and can be reimagined as bioenergy crops for renewable natural gas production and carbon (C) benefits (fossil fuel substitution and C storage). Little information is available on the large-scale adoption of winter rye for these purposes. To investigate the impacts in the North Central US, we used the Root Zone Water Quality Model (RZWQM) to simulate corn-soybean rotations with and without winter rye across 40 sites. The simulations were interpolated across a five-state area (IA, IL, IN, MN, and OH) with counties in the Mississippi River Basin, which consists of ~8 million ha with potential for rye cover crops on artificially drained corn-soybean fields (more than 63 million ha total). Harvesting fertilized rye cover crops before soybean planting in this area can reduce N loads to the Gulf of Mexico by 27% relative to no cover crops, and provide 18 million Mg yr-1 of biomass–equivalent to 0.21 EJ yr-1 of biogas energy content or 3.5 times the 2022 US cellulosic biofuel production. Capturing the CO2 in biogas from digesting rye in the region and sequestering it in underground geologic reservoirs could mitigate 7.5 million Mg CO2 yr-1. Nine clusters of counties (hotspots) were identified as an example of implementing rye as an energy cover crop on an industrial scale where 400 Gg yr-1 of rye could be sourced within a 121 km radius. Hotspots consisted of roughly 20% of the region's area and could provide ~50% of both the N loss reduction and rye biomass. These results suggest that large-scale energy cover crop adoption would substantially contribute to the goals of reducing N loads to the Gulf of Mexico, increasing bioenergy production, and providing C benefits.