The ability of sweet sorghum to be utilized as feedstock for ethanol production at high initial dry material concentration was investigated. Sweet sorghum, after being dried, was liquefacted employing commercial cellulase solution Celluclast® 1.5L, in order submerged fermentation to be permitted under high-solids concentrations. The presence of a separate enzymatic liquefaction step at 350 kg m−3 initial DM enhanced both ethanol production and productivity by 29.76% and 250%, respectively. Response surface methodology, based on the central composite design was applied to explore the combined effect of liquefaction duration and enzyme loading in order liquefaction conditions to be optimized. When the optimum conditions were tested using an enzyme load of 8.32 FPU g−1 of dry material for 8.6 h at 50 °C, high productivity (3.0 kg m−3 h−1) and final ethanol production (62.5 kg m−3) were achieved.