To improve enzymatic digestibility and sugar concentration, sweet sorghum bagasse was pretreated with alkali and liquid hot water, and then subjected to fed-batch enzymatic hydrolysis. Scanning electron microscopy assay suggested that different pretreatment methods resulted in different composition and structure of residues; these changes had a significant influence on cellulose hydrolysis. Fresh substrate was pretreated and then added at different amounts during the first 48 h to yield a final dry matter content of 30% (w/v). For liquid hot water pretreatment, a maximal glucose concentration of 95.71 g/L, corresponding to 52.85% xylan removal, was obtained with the sweet sorghum bagasse pretreated at 184°C for 18 min. NaOH soaking at ambient conditions removed lignin up to 60%, and the subsequent hydrolysis with cellulase loading of less than 10 FPU/g DM, and substrate supplementation every few hours yield the high glucose and xylose concentrations of 114.89L and 29.93 g/L, respectively after 144 h.