Meeting future biofuel targets set by the 2007 Energy Independence and Security Act (EISA) will require a substantial increase in production of corn. The Midwest, which has the highest overall crop production capacity, is likely to bear the brunt of the biofuel-driven changes. In this paper, we set forth a method for developing a possible future landscape and evaluate changes in practices and production between base year (BY) 2001 and biofuel target (BT) 2020. In our BT 2020 Midwest landscape, a total of 25 million acres (1 acre = 0.40 ha) of farmland was converted from rotational cropping to continuous corn. Several states across the Midwest had watersheds where continuous corn planting increased by more than 50%. The output from the Center for Agriculture and Rural Development (CARD) econometric model predicted that corn grain production would double. In our study we were able to get within 2% of this expected corn production. The greatest increases in corn production were in the Corn Belt as a result of conversion to continuous corn planting. In addition to changes to cropping practices as a result of biofuel initiatives we also found that urban growth would result in a loss of over 7 million acres of productive farmland by 2020. We demonstrate a method which successfully combines economic model output with gridded land cover data to create a spatially explicit detailed classification of the landscape across the Midwest. Understanding where changes are likely to take place on the landscape will enable the evaluation of trade-offs between economic benefits and ecosystem services allowing proactive conservation and sustainable production for human well-being into the future.