Bioethanol produced from renewable resource has potential to solve environmental pollution and to satisfy the need of demand and supply. It favours the use of nonfood lignocellulosic materials. Ethanol produced from plant materials can sustain the economy by reducing cost of imported petroleum, emitting neutral CO2. Moreover, it enhances the economy by providing value added market opportunities for transportation and agricultural sector. Therefore, the objective of the study was to investigate bioethanol production from stalk residues of Chiquere and Gebabe varieties of sweet sorghum collected from West Arsi Zone, Ethiopia. Response surface methods with a three factor (inoculum size, pH, and dilution rate) with triplicate run by using the Box–Behnken method was referred. The experiment employed dilute acid hydrolysis, because it is an easy and productive process by treating the stalks with 4% of sulfuric acid for effective hydrolysis of substrate. Finally, the fermentation was carried out at 30°C for 72 hours on a shaker at 180 rpm by using Saccharomyces cerevisiae. The significance of the result was evaluated by using ANOVA, where P values <0.05 were considered statistically significant. In the process, maximum yield of ethanol was obtained at an inoculum size of 5% (22.40%), pH level of 4.0 (21%), and dilution rate at 10 ml (21.46%). Very low yeast inoculum size and dilution factor have positive effect on the yield of ethanol, whereas very high dilution rate produced negative impact on ethanol production. FTIR spectroscopy peaks associated with O-H, C-O, and C-H stretching vibrations confirmed the presence of ethanol obtained from sweet sorghum stalks. The results of our study indicated that, being available in bulky amounts and nonedible material, sweet sorghum stalks can serve as potential feedstock for bioethanol production in developing countries such as Ethiopia.