The United States has mandated the production of 80 billion liters of second-generation biofuel by 2022, and several approaches to meet this target focus on using ligno-cellulosic ethanol from perennial grasses and non-food crops. The large-scale deployment of biofuel agronomy should consider high-yielding crops that meet ethanol production goals, choose appropriate landscapes for biofuel crops from a climate and food production standpoint, and a full consideration of the environmental impact of large-scale land use change. The southeastern United States has a long growing season conducive for producing high-yielding crops, and is relatively less important to US food production than the rain-fed Midwestern states that have been extensively studied for biofuel crops. We use the DayCent biogeochemical model to run simulation experiments to test the hypotheses that converting a large swath of traditional agriculture in the southeastern United States that is already utilized for bioenergy production (assuming 35% of current corn-soy, and 10% of grazed pasture hectares; similar to 950,000 ha) to energy cane will result in greater biomass production, increased soil C storage, decreased soil N losses and lower greenhouse gas emissions than a landscape of corn-soy rotations and interspersed grazed pasture. Our simulations suggest that energy cane above-ground productivity on former pasture and corn-soy fields would be between 52-59 million Mg dry mass per year, resulting in 21.1-23.7 billion liters of ligno-cellulosic ethanol, or similar to 28% of the 2022 US government mandate. DayCent did not predict significant changes in soil C flux from land conversion to energy cane, but simulations predicted lower rates of N loss compared to current agriculture. GHG emissions from energy cane landscapes were substantially higher on former pasture, but an order of magnitude lower when compared to corn-soy hectares. While further study is needed to ascertain the full economic and industrial feasibility of converting nearly 1,000,000 ha of land to energy cane production, our results suggest that such an undertaking could meet a sizeable fraction of the US ethanol mandate, reduce N pollution and GHG emissions, and avoid compromising land devoted to food production in the southeastern United States.