Cassava pulp (CP) is considered as a major and low-cost agro-industrial solid byproduct of cassava starch processing, where 48% of starch granules was still entrapped in its complex lignocellulosic matrix of cell wall structure with 21% cellulose and 8% hemicellulose. In this study, the liquid hot water (LHW) pretreatment was aimed to disrupt the cell wall structure of CP and solubilized hemicellulose and starch into saccharides to enhance biomethane production. Reaction conditions of LHW pretreatment, temperature (160–200 °C), and time (0–30 min) were optimized by response surface methodology. LHW pretreatment at 187 °C for 7 min boosted the highest level of starch and hemicellulose solubilization into the liquid phase, resulting in the maximized glucose yield of 444 mg/gCP. Starch and hemicellulose were mostly removed from CP at 99 and 79%, respectively, while 68% cellulose and 10% lignin particularly remained in solid residue. The disrupted cell wall structure and crystalline cellulose after LHW pretreatment were also observed. Microbial inhibitors such as furfural and hydroxymethylfurfural were found in low concentration at 31 and 32 μg/mL, respectively. In addition, there were no lag phase and inhibitory effect during anaerobic digestion of the pretreated CP. Biochemical methane potential of the LHW-pretreated CP showed the methane production rate and methane yield at 1.6 times and 35% higher than that of non-pretreated CP, respectively, by shortening anaerobic digestion time from 22 d to 10 d. It was shown that LHW was an efficient chemical-free method for enhancing biodegradability of CP in conversion to biomethane.