Bimetallic alloy nanoparticles (NPs) have unique electronic and geometric properties that are regarded as the origin of bimetallic synergy. However, this issue remains controversial because the surface structure, composition, and oxidation state of bimetallic NPs are altered during the catalytic reaction. Here, we investigate the formation and impact of the Pt–CoO interface on Pt–Co bimetallic NPs using state-of-the-art operando surface techniques, such as ambient-pressure X-ray photoelectron spectroscopy and diffuse reflectance infrared Fourier-transform spectroscopy. The Pt–CoO interfacial structures formed on the surface during the CO oxidation reaction play a key role in enhancing the catalytic activity. Our research indicates that the metal oxide–metal interface in bimetallic NPs provides a clue to bimetallic synergy.