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The USDA initiated the Conservation Effects Assessment Project (CEAP) to quantify the environmental benefits of conservation practices at regional and national scales. For this assessment, a sampling and modeling approach is used. This paper provides a technical overview of the modeling approach used in CEAP cropland assessment to estimate the off-site water quality benefits of conservation practices using the Ohio River Basin (ORB) as an example. The modeling approach uses a farm-scale model, Agricultural Policy Environmental Extender (APEX), and a watershed scale model (the Soil and Water Assessment Tool [SWAT]) and databases in the Hydrologic Unit Modeling for the United States system. Databases of land use, soils, land use management, topography, weather, point sources, and atmospheric depositions were developed to derive model inputs. APEX simulates the cultivated cropland, Conserve Reserve Program land, and the practices implemented on them, whereas SWAT simulates the noncultivated land (e.g., pasture, range, urban, and forest) and point sources. Simulation results from APEX are input into SWAT. SWAT routes all sources, including APEX’s, to the basin outlet through each eight-digit watershed. Each basin is calibrated for stream flow, sediment, and nutrient loads at multiple gaging sites and turned in for simulating the effects of conservation practice scenarios on water quality. Results indicate that sediment, nitrogen, and phosphorus loads delivered to the Mississippi River from ORB could be reduced by 16, 15, and 23%, respectively, due to current conservation practices. Modeling tools are useful to provide sciencebased information for assessing existing conservation programs, developing future programs, and developing insights on load reductions necessary for hypoxia in the Gulf of Mexico.