Revealing the active nature of oxide-derived copper is of key importance to understand its remarkable catalytic performance during the cathodic CO reduction reaction (CORR) to produce valuable hydrocarbons. Using advanced spectroscopy, electron microscopy, and electrochemically active surface area characterization techniques, the electronic structure and the changes in the morphology/roughness of thermally oxidized copper thin films were revealed during CORR. For this purpose, we developed an in situ cell for X-ray spectroscopy that could be operated accurately in the presence of gases or liquids to clarify the role of the initial thermal oxide phase and its active phase during the electrocatalytic reduction of CO. It was found that the Cu(I) species formed during the thermal treatment are readily reduced to Cu during the CORR, whereas Cu(II) species are hardly reduced. In addition, Cu(II) oxide electrode dissolution was found to yield a porous/void structure, where the lack of electrical connection between isolated islands prohibits the CORR. Therefore, the active/stable phase for CORR is metallic copper, independent of its initial phase, with a significant change in its morphology upon its reduction yielding the formation of a rougher surface with a higher number of underco-ordinated sites. Thus, the initial thermal oxidation of copper in air controls the reaction activity/selectivity because of the changes induced in the electrode surface morphology/roughness and the presence of more undercoordinated sites during the CORR.