In this study, core-shell Cu@Cu2O microspheres were synthesized with an interfacial hydrothermal method. The resulting products were systematically characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. A core-shell Cu@Cu2O microsphere formation mechanism, which involved the in situ transformation of Cu to Cu2O, was proposed on the basis of the characterization results. That is, pure Cu microspheres were first formed through the reduction of copper(II) acetylacetonate. Then surface Cu was oxidatively transformed to a Cu2O shell, resulting in the Cu@Cu2O core-shell structure. The content of Cu2O shell in the composite microspheres increased with prolonged reaction time. The as-prepared Cu@Cu2O core-shell microspheres exhibited enhanced photocatalytic activity as compared to Cu2O on the degradation of gaseous nitrogen monoxide under visible light irradiation. The reasons for visible-light-driven photocatalytic activity enhancement on Cu@Cu2O core-shell microspheres were discussed. These Cu@Cu2O microspheres are ideal candidates for fundamental studies as well as catalytic, electronic, and magnetic applications. © 2009 American Chemical Society.