Conventional wastewater treatment plants (CWTPs) are intensive energy consumers. New technologies are emerging for wastewater treatment such as microbial electrolysis cells (MECs) that can simultaneously treat wastewater and generate hydrogen as a renewable energy source. Mathematical modeling of single and dual-chamber microbial electrolysis cells (SMEC and DMEC) has been developed based on microbial population growth in this study. The model outputs were validated successfully with previous works, and are then used for comparisons between the SMEC and DMEC regarding the hydrogen production rate (HPR). The results reveal that the daily HPR in DMEC is higher than in SMEC, with about 0.86 l H2 and 0.52 l H2, respectively, per 1 L of wastewater. Moreover, the results have been used to compare the HPR in water electrolysis (WE) processes and MECs. WE consume 51 kWh to generate 1 kg of hydrogen, while SMEC and DMEC require only 30 kWh and 24.5 kWh, respectively.