Tuning an oxide/metal interface is of critical importance for the performance enhancement of many heterogeneous catalytic reactions. However, catalytic oxidation occurring at the interface between non-reducible oxide and metal has been challenging, since non-reducible oxides hardly lose their lattice oxygen (O L ) or dissociate O 2 from the gas phase. In this work, a ZnO monolayer film on Au(111) is used as an inverse catalyst to investigate CO oxidation occurring at the ZnO/Au(111) interface via high pressure scanning tunneling microscopy. Surface science experiments indicate that oxygen intercalation under the ZnO monolayer film, termed ZnO/O/Au(111), can be achieved via a surface reaction with 1 × 10 -6 mbar O 3 . Subsequent exposure of the formed ZnO/O/Au(111) surface to mbar CO at room temperature leads to the recovery of the pristine ZnO/Au(111) surface. Theoretical calculations reveal that O L adjacent to intercalated oxygen (O int ) is activated due to the O L -Zn-O int bonding and surface corrugation, which can be directly involved in CO oxidation. Subsequently, O int migrates to the formed oxygen vacancy from the subsurface resuming the pristine ZnO structure. These results thus reveal that oxygen intercalation underneath single-layer ZnO will strongly boost the oxidation reaction via activating adjacent lattice oxygen atoms.