Progress on reducing nutrient loss from annual croplands has been hampered by perceived conflicts between short-term profitability and long-term stewardship, but these may be overcome through strategic integration of perennial crops. Perennial biomass crops like switchgrass can mitigate nitrate-nitrogen (NO3-N) leaching, address bioenergy feedstock targets, and – as a lower-cost management alternative to annual crops (i.e., corn, soybeans) – may also improve farm profitability. We analyzed publicly available environmental, agronomic, and economic data with two integrated models: a subfield agroecosystem management model, Landscape Environmental Assessment Framework (LEAF), and a process-based biogeochemical model, DeNitrification-DeComposition (DNDC). We constructed a factorial combination of profitability and NO3-N leaching thresholds and simulated targeted switchgrass integration into corn/soybean cropland in the agricultural state of Iowa, USA. For each combination, we modeled (i) area converted to switchgrass, (ii) switchgrass biomass production, and (iii) NO3-N leaching reduction. We spatially analyzed two scenarios: converting to switchgrass corn/soybean cropland losing >US$ 100 ha−1 and leaching >50 kg ha−1 (‘conservative’ scenario) or losing >US$ 0 ha−1 and leaching >20 kg ha−1 (‘nutrient reduction’ scenario). Compared to baseline, the ‘conservative’ scenario resulted in 12% of cropland converted to switchgrass, which produced 11 million Mg of biomass and reduced leached NO3-N 18% statewide. The ‘nutrient reduction’ scenario converted 37% of cropland to switchgrass, producing 34 million Mg biomass and reducing leached NO3-N 38% statewide. The opportunity to meet joint goals was greatest within watersheds with undulating topography and lower corn/soybean productivity. Our approach bridges the scales at which NO3-N loss and profitability are usually considered, and is informed by both mechanistic and empirical understanding. Though approximated, our analysis supports development of farm-level tools that can identify locations where both farm profitability and water quality improvement can be achieved through the strategic integration of perennial vegetation.