This study reports a breakthrough in electrochemical synthesis of hydrogen peroxide (H₂O₂) from mixed dioxygen (O₂/N₂) gas, bypassing the Le Chatelier principle. The key innovation is the creation of single-zinc vacancies in a zinc oxide (ZnO) crystal, which enables an enzyme-like binding of the catalyst with high selectivity to O₂. This leads to a shift from the Langmuir-Hinshelwood mechanism to the Eley-Rideal mechanism, enhancing reaction efficiency. The ER-ZnO catalyst demonstrates remarkable performance, maintaining stable H₂O₂ yields and Faradaic efficiencies across a wide range of O₂ concentrations (100% to 21%), even at high current densities (50-300 mA cm⁻²). The prototype device achieves a Faradaic efficiency of 87.8% at 320 mA cm⁻², surpassing state-of-the-art catalysts and approaching the theoretical limit for direct air electrolysis. Techno-economic analysis shows that using atmospheric air as a feedstock reduces production costs by 21.7% compared to high-purity O₂, with the lowest H₂O₂ capital cost at 0.3 K g⁻¹. The findings challenge the classical Le Chatelier principle, offering new insights into designing catalytic systems beyond traditional constraints. The study highlights the importance of catalyst structure in achieving high selectivity and efficiency in oxygen reduction reactions, with implications for sustainable hydrogen peroxide production and electrochemical systems.This study reports a breakthrough in electrochemical synthesis of hydrogen peroxide (H₂O₂) from mixed dioxygen (O₂/N₂) gas, bypassing the Le Chatelier principle. The key innovation is the creation of single-zinc vacancies in a zinc oxide (ZnO) crystal, which enables an enzyme-like binding of the catalyst with high selectivity to O₂. This leads to a shift from the Langmuir-Hinshelwood mechanism to the Eley-Rideal mechanism, enhancing reaction efficiency. The ER-ZnO catalyst demonstrates remarkable performance, maintaining stable H₂O₂ yields and Faradaic efficiencies across a wide range of O₂ concentrations (100% to 21%), even at high current densities (50-300 mA cm⁻²). The prototype device achieves a Faradaic efficiency of 87.8% at 320 mA cm⁻², surpassing state-of-the-art catalysts and approaching the theoretical limit for direct air electrolysis. Techno-economic analysis shows that using atmospheric air as a feedstock reduces production costs by 21.7% compared to high-purity O₂, with the lowest H₂O₂ capital cost at 0.3 K g⁻¹. The findings challenge the classical Le Chatelier principle, offering new insights into designing catalytic systems beyond traditional constraints. The study highlights the importance of catalyst structure in achieving high selectivity and efficiency in oxygen reduction reactions, with implications for sustainable hydrogen peroxide production and electrochemical systems.