Monopolar membrane-assisted electrolyzers enable water electrolysis using acid-alkali asymmetric electrolytes. However, understanding how such an electrolyzer works remains a significant challenge. By assessing the concentration-polarization state in membranes, measuring the ion concentration change in electrolytes, and determining the corresponding transmembrane resistance, we reveal that this electrolyzer can prevent the negative effect of the water dissociation process. The electrolyzer functions by the chemical potential gradient between the asymmetric electrolytes. Briefly, the delta in pH between asymmetric electrolytes significantly modifies the reversible hydrogen electrode potential at both electrolyte compartments and electrodes, and therefore decreases the required external potential. Notably, the unavoidable ion diffusion slightly reduces this positive effect. The electrolyzer performance depends on the membrane property, working temperature, electrolyte compositions as well as electrocatalysts. When adopted with state-of-the-art electrocatalysts, this electrolyzer achieves an industrially relevant current density of 200 mA cm−2 at a cell voltage of only 1.39 V, outperforming most conventional water electrolyzers, and to the best of our knowledge also those fed by asymmetric electrolytes. Overall, this work highlights the promise of coupling chemical potential energy and electrical energy for hydrogen production, which provides a new strategy to lower the potential for driving water splitting. Display omitted •Monopolar membrane-assisted electrolyzers exhibit superior performance.•The chemical potential gradient between asymmetric electrolytes plays a major role.•The membrane, working temperature and electrolyte compositions affect the activity.•The electrolyzer is easily scalable and highly flexible in electrolyte type.