While biofuels may yield renewable fuel benefits, there could be downsides in terms of water quality and other environmental stressors, particularly if corn is relied upon exclusively as the feedstock. In this article, we describe a modeling system that links agricultural land use decisions in the Upper Mississippi River Basin (UMRB) to economic drivers. This modeling system is then used to assess several scenarios to identify the water quality effects of alternative land uses and the impacts of introducing on the landscape alternative feedstocks, such as switchgrass, to support renewable energy goals. Specifically, a scenario that assesses the water quality effects associated with an increase in corn acreage due to higher relative corn prices provides an estimate of the water quality effects that current biofuel policies may have in the UMRB. Since cellulosic alternatives such as switchgrass are not currently technologically feasible, we undertake two additional scenarios to assess the prices needed to induce switchgrass production in the watershed and the associated water quality changes. Switchgrass production has sizable benefits in terms of sediment and phosphorus losses, though targeting does little to improve sediment over the unrestricted location of switchgrass. Nitrate losses are still high, likely because of the high fertilization levels assumed. Our analysis can help evaluate the costs and environmental impacts associated with implementation strategies for the biofuel mandates of the new energy bill.