High-entropy catalysts featuring exceptional properties are, in no doubt, playing an increasingly significant role in aprotic lithium-oxygen batteries. Despite extensive effort devoted to tracing the origin of their unparalleled performance, the relationships between multiple active sites and reaction intermediates are still obscure. Here, enlightened by theoretical screening, we tailor a high-entropy perovskite fluoride (KCoMnNiMgZnF3-HEC) with various active sites to overcome the limitations of conventional catalysts in redox process. The entropy effect modulates the d-band center and d orbital occupancy of active centers, which optimizes the d–p hybridization between catalytic sites and key intermediates, enabling a moderate adsorption of LiO2 and thus reinforcing the reaction kinetics. As a result, the Li–O2 battery with KCoMnNiMgZnF3-HEC catalyst delivers a minimal discharge/charge polarization and long-term cycle stability, preceding majority of traditional catalysts reported. These encouraging results provide inspiring insights into the electron manipulation and d orbital structure optimization for advanced electrocatalyst.