Excessive nutrients transported from the Mississippi River Basin (MRB) have created a hypoxic zone within the Gulf of Mexico, with numerous negative ecological effects. Furthermore, federal expenditures on agricultural conservation practices have received intense scrutiny in recent years. Partly driven by these factors, the USDA Conservation Effects Assessment Project (CEAP) recently completed a comprehensive evaluation of nutrient sources and delivery to the Gulf. The modeling framework used in the CEAP Cropland National Assessment, or Cropland CEAP, consists of the Agricultural Policy/Environmental eXtender (APEX) and Soil and Water Assessment Tool (SWAT) models. This CEAP modeling framework was successfully calibrated for flow, sediment, and nutrients at 38 sites and validated at an additional 17. Simulation results indicated that cultivated cropland was the dominant source of nitrogen (N) and phosphorus (P) to both local waters and the Gulf, but this was not true for each water resource region within the MRB. In addition, the results showed that point sources remain significant contributors of P loads, especially in the Tennessee and Arkansas/Red River basins where point source P loads exceeded those from cultivated cropland. Similarly, urban nonpoint sources were significant nutrient sources. The Upper Mississippi, Lower Mississippi, and Ohio basins contributed the largest amounts of nutrients delivered to the Gulf. The high delivery areas near the Mississippi River main stem, from which 87% of N and 90% of P was predicted to reach the Gulf, also coincided with elevated nutrient yields to local waters. Conservation practices established on agricultural lands within the MRB were predicted to have reduced nutrient loads to the Gulf by 20% as compared with a no conservation condition. The results indicate the importance of targeted implementation of conservation practices and consideration of local water and/or Gulf impacts depending on program goal(s). The present application illustrates the value of the Cropland CEAP modeling framework as a useful, science-based tool to evaluate pollutant sources and delivery and effects of agricultural conservation practices.