The oxygen evolution reaction is known to be a kinetic bottleneck for water splitting. Triggering the lattice oxygen oxidation mechanism (LOM) can break the theoretical limit of the conventional adsorbate evolution mechanism and enhance the oxygen evolution reaction kinetics, yet the unsatisfied stability remains a grand challenge. Here, we report a high-entropy MnFeCoNiCu layered double hydroxide decorated with Au single atoms and O vacancies (Au_SA-MnFeCoNiCu LDH), which not only displays a low overpotential of 213 mV at 10 mA cm⁻² and high mass activity of 732.925 A g⁻¹ at 250 mV overpotential in 1.0 M KOH, but also delivers good stability with 700 h of continuous operation at ~100 mA cm⁻². Combining the advanced spectroscopic techniques and density functional theory calculations, it is demonstrated that the synergistic interaction between the incorporated Au single atoms and O vacancies leads to an upshift in the O 2p band and weakens the metal-O bond, thus triggering the LOM, reducing the energy barrier, and boosting the intrinsic activity.