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Nutrient runoff from agricultural regions of the midwestern U.S. corn belt has degraded water quality in many inland and coastal water bodies such as the Great Lakes and Gulf of Mexico. Under current climate, observational studies have shown that winter cover crops can reduce dissolved nitrogen and phosphorus losses from row-cropped agricultural watersheds, but performance of cover crops in response to climate variability and climate change has not been systematically evaluated. Using the Soil & Water Assessment Tool (SWAT) model, calibrated using multiple years of field-based data, we simulated historical and projected future nutrient loss from two representative agricultural watersheds in northern Indiana, USA. For 100% cover crop coverage, historical simulations showed a 31–33% reduction in nitrate (NO3−) loss and a 15–23% reduction in Soluble Reactive Phosphorus (SRP) loss in comparison with a no-cover-crop baseline. Under climate change scenarios, without cover crops, projected warmer and wetter conditions strongly increased nutrient loss, especially in the fallow period from Oct to Apr when changes in infiltration and runoff are largest. In the absence of cover crops, annual nutrient losses for the RCP8.5 2080s scenario were 26–38% higher for NO3−, and 9–46% higher for SRP. However, the effectiveness of cover crops also increased under climate change. For an ensemble of 60 climate change scenarios based on CMIP5 RCP4.5 and RCP8.5 scenarios, 19 out of 24 ensemble-mean simulations of future nutrient loss with 100% cover crops were less than or equal to historical simulations with 100% cover crops, despite systematic increases in nutrient loss due to climate alone. These results demonstrate that planting winter cover crops over row-cropped land areas constitutes a robust climate change adaptation strategy for reducing nutrient losses from agricultural lands, enhancing resilience to a projected warmer and wetter winter climate in the midwestern U.S.