Butanol represents a high-energy-density advanced biofuel with superior compatibility to conventional fuel infrastructures and broad industrial significance. As a promising second-generation biofuel, biobutanol is predominantly produced via acetone–butanol–ethanol (ABE) fermentation by solventogenic Clostridium species. This chapter focuses on biobutanol production from lignocellulosic agricultural residues, a non-food and sustainable feedstock. It illustrates the composition of lignocellulosic hydrolysates and the inhibitory effects of toxic byproducts on microbial metabolism and butanol biosynthesis. Key strategies including detoxification technologies, metabolic engineering for improved sugar co-utilization and stress tolerance, and consolidated bioprocessing (CBP) are systematically reviewed. Integration of strain engineering and process optimization significantly enhances fermentation efficiency and butanol productivity. The utilization of lignocellulosic biomass enables cost-effective, low-carbon, and sustainable biobutanol production, demonstrating great potential for industrial application and future bioenergy development.