The urea oxidation reaction (UOR) is a promising alternative to the oxygen evolution reaction (OER) for sustainable hydrogen production due to its lower onset potential. However, the reasons behind this advantage remain unclear, with inconsistencies in the literature regarding the UOR mechanism. Previously, UOR was mostly believed to proceed via a six-electron pathway producing N2 and CO2, but this assumption lacked experimental and theoretical validation. Here, the UOR mechanism is thoroughly re-evaluated by integrating experimental observations and density functional theory calculations on β-NiOOH catalyst as a model system. Experimentally, significant UOR current densities of 100 and 500 mA cm−2 were achieved at potentials of 1.40 and 1.53 V RHE, respectively, outperforming the OER, which required 1.79 V RHE at 500 mA cm−2. Theoretical calculations reveal that oxygen vacancies are thermodynamically favored and serve as preferential adsorption sites for urea, with a significantly lower energy barrier (1.49 eV) compared to the OER (3.25 eV). OCN− and NO2− were identified as the primary reaction products, which were also confirmed experimentally. This work not only clarifies the UOR pathway and the critical role of oxygen vacancies in enhancing reaction selectivity and efficiency but also resolves longstanding mechanistic ambiguities, providing a foundation for the rational design of advanced electrocatalysts for efficient hydrogen production and environmental remediation.​