Driven by biofuel policies, which aim to reduce greenhouse gas (GHG) emissions and increase domestic energy supply, global production and consumption of bioethanol have doubled between 2007 and 2016, with rapid growth in corn-based bioethanol in the U.S. and sugar cane-based bioethanol in Brazil. Advances in crop yields, energy use efficiency in fertilizer production, biomass-to-ethanol conversion rates, and energy efficiency in ethanol production have improved the energy balance and GHG emission reduction potential of bioethanol. In the current study, the water, energy, and carbon footprints of bioethanol from corn in the U.S. and sugar cane in Brazil were assessed. The results show that U.S. corn bioethanol has a smaller water footprint (541 L water/L bioethanol) than Brazilian sugar cane bioethanol (1115 L water/L bioethanol). Brazilian sugar cane bioethanol has, however, a better energy balance (17.7 MJ/L bioethanol) and smaller carbon footprint (38.5 g CO2e/MJ) than U.S. bioethanol, which has an energy balance of 11.2 MJ/L bioethanol and carbon footprint of 44.9 g CO2e/MJ. The results show regional differences in the three footprints and highlight the need to take these differences into consideration to understand the implications of biofuel production for local water resources, net energy production, and climate change mitigation.