Developing advanced water electrolysis technology to promote large-scale hydrogen production is an effective way to alleviate the current energy crisis and environmental pollution. Traditional water electrolysis technology faces some issues, such as the slow oxygen evolution reaction (OER) kinetics, high energy consumption, the low added value of O2, and reactive oxygen species degradation membrane, which limit its large-scale application. Replacing the OER by anode reaction with a lower energy barrier via the reaction design can reduce the energy consumption of the electrolysis process and obtain high-value-added oxidation products, which have significant economic benefits and development potential. This review summarizes recent advances in the sacrificial agent oxidation reaction (SAOR) and electrochemical synthesis reaction (ESR) in replacing the OER and classifies these two types of replacement reactions. The corresponding oxidation mechanism, suitable non-noble metal-based catalysts, and associated optimization strategies are reviewed. In addition, possible challenges and future directions for developing energy-saving hybrid water electrolysis systems driven by high-performance catalysts are outlined.