Annual U.S. production of bioethanol, primarily produced from corn starch in the U.S. Midwest, rose to 57 billion liters in 2021, which fulfilled the required conventional biofuel target set forth by the Energy Independence and Security Act (EISA) of 2007. At the same time, the U.S. fell short of the cellulosic or advanced biofuel target of 79 billion liters. The growth of bioenergy grasses (e.g., Miscanthus and switchgrass) across the Central and Eastern U.S. has the potential to feed enhanced cellulosic bioethanol production and, if successful, increase renewable fuel volumes. However, water consumption and climate change and its extremes are critical concerns in corn and bioenergy grass productivity. These concerns are compounded by the demands on potentially productive land areas and water devoted to producing biofuels. This is a fundamental Food-Energy-Water System (FEWS) nexus challenge. We apply a computational framework to estimate potential bioenergy yield and conversion to bioethanol yield across the U.S., based on crop field studies and conversion technology analysis for three crops—corn, Miscanthus, and two cultivars of switchgrass (Cave-in-Rock and Alamo). The current study identifies regions where each crop has its highest yield across the Center and Eastern U.S. While growing bioenergy grasses requires more water than corn, one advantage they have as a source of bioethanol is that they control nitrogen leaching relative to corn. Bioenergy grasses also maintain steadily high productivity under extreme climate conditions, such as drought and heatwaves in the year 2012 over the U.S. Midwest, because the perennial growing season and the deeper and denser roots can ameliorate the soil water stress. While the potential ethanol yield could be enhanced using energy grasses, their practical success in becoming a potential source of ethanol yield remains limited by socio-economic and operational constraints and concerns regarding competition with food production.