The growth of the cellulosic ethanol industry is currently impeded by high production costs. One possible solution is to improve the performance of fermentation itself, which has great potential to improve the economics of the entire production process. Here, we demonstrated significantly improved productivity through application of an advanced fermentation approach, named self-cycling fermentation (SCF), for cellulosic ethanol production.The flow rate of outlet gas from the fermenter was used as a real-time monitoring parameter to drive the cycling of the ethanol fermentation process. Then, long-term operation of SCF under anaerobic conditions was improved by the addition of ergosterol and fatty acids, which stabilized operation and reduced fermentation time. Finally, an automated SCF system was successfully operated for 21 cycles, with robust behavior and stable ethanol production. SCF maintained similar ethanol titers to batch operation while significantly reducing fermentation and down times. This led to significant improvements in ethanol volumetric productivity (the amount of ethanol produced by a cycle per working volume per cycle time)-ranging from 37.5 to 75.3%, depending on the cycle number, and in annual ethanol productivity (the amount of ethanol that can be produced each year at large scale)-reaching 75.8 ± 2.9%. Improved flocculation, with potential advantages for biomass removal and reduction in downstream costs, was also observed.Our successful demonstration of SCF could help reduce production costs for the cellulosic ethanol industry through improved productivity and automated operation.