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Abstract: Cellulosic biofuels face significant problems of feedstock aggregation and logistics leading to poor economies of scale. The current model is for relatively small biorefineries using feedstock gathered locally. Here a depot‐based decentralized biorefinery system is explored to estimate the US Energy Independence and Security Act (EISA) compliant corn stover ethanol production potential in the US Midwest. Depots serve to aggregate, pretreat, and densify biomass (via pellets) and thereby enable very large biorefineries using a decentralized system to collect these pellets. Such a corn‐stover based decentralized system using depots would establish one or two very large‐scale decentralized biorefineries capable of processing about 8–12% of the total corn stover available in the US Midwest. These decentralized biorefineries are economically competitive with the centralized biorefineries. About 55–153 depots could supply the pretreated pellets to the individual decentralized biorefineries leading to an annual production of 1.02–2.91 billion liters of cellulosic ethanol fuel. Most of the participating depots are located in Illinois and Iowa. The total EISA‐compliant ethanol fuel produced in the decentralized system is 2.82–4.07 billion liters per year. The ethanol selling price in the depot‐based decentralized biorefinery system varies between US$0.67 and US$0.72 L−1. The greenhouse gas (GHG) savings from cellulosic ethanol in the decentralized system compared to gasoline are 3.35–4.84 Tg CO2 year−1. Importantly, the total capital investment per annual volume of ethanol in the decentralized biorefinery ranges from US$0.71 L1 to US$1.15 L1, while the total capital investment per annual ethanol volume in the centralized biorefinery is US$1.98 L−1. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]