In the US, 95% of biofuel is produced from corn (Zea mays L), an intensively managed annual crop that is also grown for food and animal feed. Using the DAYCENT model, we estimated the effects on ecosystem services of replacing corn ethanol feedstocks with the perennial cellulosic feedstocks switchgrass (Panicum virgatum L) and miscanthus (Miscanthus × giganteus Greef et Deuter). If cellulosic feedstocks were planted on cropland that is currently used for ethanol production in the US, more ethanol (+82%) and grain for food (+4%) could be produced while at the same time reducing nitrogen leaching (−15 to −22%) and greenhouse-gas (GHG) emissions (−29 to −473%). The GHG reduction was large even after accounting for emissions associated with indirect land-use change. Conversion from a high-input annual crop to a low-input perennial crop for biofuel production can thus transition the central US from a net source to a net sink for GHGs.