The introduction of high-entropy and high specific surface area into Prussian blue analogues (PBAs) has yet to create interest in the field of electrocatalytic small-molecule oxidation reactions. Herein, we synthesize a novel class of high-entropy (HE) PBAs with a high specific surface area via a simple NH3·H2O-etching strategy and systematically investigate the electrocatalytic performance of HE-PBA toward electrocatalytic water, ethanol, and urea oxidation reactions. Importantly, the NH3·H2O-etched HE-PBA (denoted as HE-PBA-e) demonstrated enhanced electrocatalytic performance toward small-molecule oxidation compared to the pristine HE-PBA, reaching 10 mA cm-2 with potentials of 1.56, 1.41, and 1.37 V for the oxygen evolution reaction (OER), ethanol oxidation reaction (EOR), and urea oxidation reaction (UOR), respectively. Deep characterizations suggest that the NH3·H2O etching treatment not only creates rich nanopores to enlarge the surface area and boosts the mass transport and electron transfer but also facilitates the formation of high-valence metal oxides to improve the intrinsic activity. This demonstration of how systematically increasing the high oxidation state of metals will serve as a governing principle for the rational design of more advanced HE-PBAs toward the electrooxidation of small molecules.