Renewable energy sources are prospective solutions for addressing future energy needs arising from the ever-increasing population and dwindling petroleum reserves. Biobutanol is one of the most efficient biofuels for use as a mixture with motor vehicle fuels. Biobutanol is produced from the acetone-butanol-ethanol (ABE) fermentation process and is separated into the pure components via multicomponent distillation. Mathematical modelling of the continuous multicomponent distillation of ABE was carried herein out using an equilibrium-based model with the modified Hang-Wanke method in MATLAB R2020a programming language and compared with the simulation results using Aspen Plus V9. The variables of this study were the feed stage, number of trays, reflux ratio to butanol purity, butanol recovery, and energy load of the reboiler and condenser. Based on the simulation results, the operating conditions in columns 1 and 2 were recommended based on the butanol purity, recovery, and reboiler load; the recommended operating conditions for column 1 are as follows—feed stage: 4, reflux ratio: 4, number of trays: 20 trays, with a column efficiency of 55.43%. The recommended operating conditions for column 2 are as follows—feed stage: 2, reflux ratio: 0.4, number of trays: up to 10, with a column efficiency of 54.94%.