This study integrates a biophysical model with a county-specific economic analysis of breakeven prices of bioenergy crop production to assess the biophysical and economic potential of biofuel production in the Midwestern United States. The bioenergy crops considered in this study include a genotype of Miscanthus, Miscanthus×giganteus, and the Cave-in-Rock breed of switchgrass (Panicum virgatum). The estimated average peak biomass yield for miscanthus in the Midwestern states ranges between 7 and 48 metric tons dry matter per hectare per year ( t DM ha−1 yr−1), while that for switchgrass is between 10 and 16 t DM ha−1 yr−1. With the exception of Minnesota and Wisconsin, where miscanthus yields are likely to be low due to cold soil temperatures, the yield of miscanthus is on average more than two times higher than yield of switchgrass. We find that the breakeven price, which includes the cost of producing the crop and the opportunity cost of land, of producing miscanthus ranges from $53 t−1 DM in Missouri to $153 t−1 DM in Minnesota in the low-cost scenario. Corresponding costs for switchgrass are $88 t−1 DM in Missouri to $144 t−1 DM in Minnesota. In the high-cost scenario, the lowest cost for miscanthus is $85 t−1 DM and for switchgrass is $118 t−1 DM, both in Missouri. These two scenarios differ in their assumptions about ease of establishing the perennial crops, nutrient requirements and harvesting costs and losses. The differences in the breakeven prices across states and across crops are mainly driven by bioenergy and row crop yields per hectare. Our results suggest that while high yields per unit of land of bioenergy crops are critical for the competitiveness of bioenergy feedstocks, the yields of the row crops they seek to displace are also an important consideration. Even high yielding crops, such as miscanthus, are likely to be economically attractive only in some locations in the Midwest given the high yields of corn and soybean in the region.