The Energy Independence and Security Act of 2007 set an annual US national production goal of 39.7 billion l of cellulosic ethanol by 2020. This paper explores the possibility of meeting that target by growing and processing Miscanthus × giganteus. We define and assess six production scenarios in which active cropland and/or Conservation Reserve Program land are used to grow to Miscanthus. The crop and biorefinery locations are chosen with consideration of economic, land-use, water management and greenhouse gas (GHG) emissions reduction objectives. Using lifecycle assessment, the net GHG footprint of each scenario is evaluated, providing insight into the climate costs and benefits associated with each scenario's objectives. Assuming that indirect land-use change is successfully minimized or mitigated, the results suggest two major drivers for overall GHG impact of cellulosic ethanol from Miscanthus: (a) net soil carbon sequestration or emissions during Miscanthus cultivation and (b) GHG offset credits for electricity exported by biorefineries to the grid. Without these factors, the GHG intensity of bioethanol from Miscanthus is calculated to be 11–13 g CO2-equivalent per MJ of fuel, which is 80–90% lower than gasoline. Including soil carbon sequestration and the power-offset credit results in net GHG sequestration up to 26 g CO2-equivalent per MJ of fuel.