Prussian blue analogues (PBAs) have emerged as efficient catalysts for oxygen evolution reaction (OER) due to their porous structure with well-dispersed active sites. However, Co-based PBA (Co-PBA) electrocatalysts are characterized by moderate OER kinetics. In this study, we developed a facile high-yield strategy to fabricate defective Co-PBA (D-Co-PBA) with [Fe(CN)6] vacancies and exposed Co (III) active sites by post-oxidation treatment of the pristine Co-PBA with aqueous H2O2. Rietveld refinement results show that the lattice parameter (a) and unit-cell volume (V) of D-Co-PBA are smaller than those of the pristine Co-PBA, thereby confirming the generation of [Fe(CN)6] vacancies. Density functional theory calculations reveal that the [Fe(CN)6] vacancy can effectively regulate the electronic structure of D-Co-PBA; this condition reduces the reaction barrier of the rate-determining step toward OER. In OER, the D-Co-PBA catalyst achieves a lower overpotential of 400 mV at a current density of 10 mA cm−2, which is superior to that of Ir/C (430 mV) and Co-PBA (450 mV). A hybrid sodium–air battery assembled with Pt/C and D-Co-PBA catalysts displays a discharge voltage of 2.75 V, an ultralow charging–discharging gap of 0.15 V, and a round-trip efficiency of 94.83% on the 1000th cycle at the current density of 0.01 mA cm−2. This study is highly promising for large-scale production of affordable and effective PBA-based materials with desirable OER activity for metal-air batteries and water-alkali electrolyzers, thus helping achieve the goal of sustainability.