Corn (Zea mays L.) stover has been identified as a prime feedstock for biofuel production in the U.S. Corn Belt because of its perceived abundance and availability, but long-term stover harvest effects on regional nutrient budgets have not been evaluated. We defined the minimum stover requirement (MSR) to maintain current soil organic carbon levels and then estimated current and future soil carbon (C), nitrogen (N), phosphorus (P), and potassium (K) budgets for various stover harvest scenarios. Analyses for 2006 through 2010 across the entire Corn Belt indicated that currently, 28 Tg or 1.6 Mg ha⁻¹ of stover could be sustainably harvested from 17.95 million hectares (Mha) with N, P, and K removal of 113, 26, and 47 kg ha⁻¹, respectively, and C removal for that period was estimated to be 4.55 Mg C ha⁻¹. Assuming continued yield increases and a planted area of 26.74 Mha in 2050, 77.4 Tg stover (or 2.4 Mg ha⁻¹) could be sustainably harvested with N, P, and K removal of 177, 37, and 72 kg ha⁻¹, respectively, along with C removal of ∼6.57 Mg C ha⁻¹. Although there would be significant variation across the region, harvesting only the excess over the MSR under current fertilization rates would result in a small depletion of soil N (−5 ± 27 kg ha⁻¹) and K (−20 ± 31 kg ha⁻¹) and a moderate surplus of P (36 ± 18 kg ha⁻¹). Our 2050 projections based on continuing to keep the MSR, but having higher yields indicate that soil N and K deficits would become larger, thus emphasize the importance of balancing soil nutrient supply with crop residue removal.