Abstract <p>Butanol synthesis from waste figs was studied using sequential mesophilic and thermophilic fermentations in a single reactor with a consolidated bioprocess approach. First, the impact of gas type was examined, then the effects of four major operating factors on butanol synthesis in the mesophilic stage were studied using two sets of Box-Wilson statistical experimental designs. Initial fig concentration (0–30&#xa0;g/L) and CO₂ pressure amount (0.1–1.5&#xa0;bar, i.e., 10–150&#xa0;kPa) on butanol synthesis were explored in the first set of experiments, while the effects of inoculation ratio (1–10%, v/v) and retention period (24–120&#xa0;h) were investigated in the second set. The butanol concentration obtained at the end of the thermophilic stage was determined as the objective function. The optimal butanol production conditions were established with high reliability using the model functions acquired from the first and second sets of tests, and verification experiments confirmed the models’ accuracy. Accordingly, the highest butanol generation was determined to be 0.6&#xa0;g/L at 22.5&#xa0;g/L fig, 1&#xa0;bar (100&#xa0;kPa) CO₂, 5% inoculum ratio, and 88&#xa0;h of mesophilic fermentation retention time. The linear and quadratic terms of the model functions were shown to have a statistically significant effect on the objective function rather than the interaction terms.</p> Graphical Abstract <p></p>