Efficient yet economic production of biofuel(s) using varied second-generation feedstock needs to be explored in the current scenario to cope up with global fuel demand. Hence, the present study was performed to reveal the use of cauliflower waste for acetone–butanol–ethanol (ABE) production using Clostridium acetobutylicum NRRL B 527. The proximate analysis of cauliflower waste demonstrated to comprise 17.32% cellulose, 9.12% hemicellulose, and 5.94% lignin. Drying of cauliflower waste was carried out in the temperature range of 60–120 °C to investigate its effect on ABE production. The experimental drying data were simulated using moisture diffusion control model. The cauliflower waste dried at 80 °C showed maximum total sugar yield of 26.05 g L−1. Furthermore, the removal of phenolics, acetic acid, and total furans was found to be 90–97, 10–40, and 95–97%, respectively. Incidentally, maximum ABE titer obtained was 5.35 g L−1 with 50% sugar utilization.