Different strategies were assessed for the production of ethanol from Agave lechuguilla that was pretreated by autohydrolysis. Separate hydrolysis and fermentation (SHF) was compared against simultaneous processes including simultaneous saccharification and fermentation (SSF) and prehydrolysis and simultaneous saccharification and fermentation (PSSF) using different solids (15%, 20%, and 25% w/w) and enzyme loadings (15 FPU/g, 20 FPU/g, and 25 FPU/g glucan). The results showed that the maximum ethanol concentration (53.7 g/L) and productivity (1.49 g/L h-1) was obtained at 36 h in the SHF configuration at the highest solids and enzyme loadings (25% w/v and 25 FPU/g glucan, respectively). The ethanol concentration and productivity obtained in the PSSF configuration at the same time were 45 g/L and 1.25 g/L h-1, respectively. The SSF configuration exhibited the lowest ethanol concentration and productivity (10.4 g/L and 0.29 g/L h-1, respectively) at 36 h. The enzyme used, Cellic CTec3, allowed for high glucose yields at the lower enzyme dosage assessed. The SHF configuration exhibited the best results. However, the PSSF configuration can be considered an attractive alternative because it eliminated the need for solid-liquid separation devices, which simplifies the industrial implementation of the process.