Efficient pretreatment is essential for overcoming lignocellulosic biomass recalcitrance and enabling its use in biotechnological processes. In this study, corncob, an agricultural by-product rich in cellulose and hemicellulose, was subjected to acid pretreatment to remove hemicellulose and subsequently delignified using two deep eutectic solvent (DES) systems: choline chloride:urea and choline chloride:glycerol. The effect of temperature and reaction time was evaluated for both systems; ChCl:U was selected for optimization due to its superior lignin removal performance under the conditions evaluated. Temperature, time, and solid–liquid ratio (SLR) were optimized using a Box–Behnken design to maximize lignin removal. Under optimal conditions (113 °C, 5.7 h, 1:16.2 g/mL), 59.086% lignin removal was achieved. Temperature and reaction time significantly influenced delignification, whereas the solid–liquid ratio had a minimal effect. Structural changes in biomass throughout the process were characterized by compositional analysis, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), confirming effective delignification. To the best of our knowledge, there are few studies that comprehensively characterize DES-treated corncob using FTIR and SEM analysis. These findings demonstrate that choline chloride:urea has potential as a sustainable and effective pretreatment system for lignocellulosic biorefineries based on agricultural residues.