AbstractRechargeable Li–O2 batteries are promising due to their superior high energy density but subject to sluggish oxygen reduction/evolution kinetics. Developing highly efficient catalysts to improve catalytic activity and alleviate oxidation–reduction overpotential of Li–O2 batteries is of great challenge and importance. Herein, a CO2‐assisted thermal‐reaction strategy is developed to fabricate isolated semi‐metallic selenium single‐atom‐doped Ti3C2 MXene catalyst (SASe‐Ti3C2) as cathodes for high‐performance Li–O2 batteries. The isolated moieties of single Se atom catalysis centers can function as active catalytic centers to drastically enhance the intrinsic LiO2‐absorption ability and thus fundamentally modulate the formation/decomposition mechanism of lithium peroxide (Li2O2) discharge product, thus demonstrating greatly enhanced redox kinetics and efficiently ameliorated overpotentials. Theoretical simulations reveal that the interaction between Se‐involved moieties and Ti3C2 substrate greatly enhances the intrinsic LiO2‐absorption ability and fundamentally promotes the charge transfer between electrode and Li2O2 product, deeply ameliorating the round‐trip overpotential. The well‐designed SASe–Ti3C2 electrode exhibits decreased charge/discharge polarization (1.10 V vs Li/Li+), ultrahigh discharge capacity (17 260 mAh g−1 at 100 mA g−1), and superior durability (170 cycles at 200 mA g−1) as cathode for Li–O2 batteries. The promising results will shed light on the design of highly efficient catalysts for oxygen‐involved systems of future investigation.