Electrochemical reduction of carbon dioxide (CO) into sustainable fuels and base chemicals requires precise control over and understanding of activity, selectivity and stability descriptors of the electrocatalyst under operation. Identification of the active phase under working conditions, but also deactivation factors after prolonged operation, are of the utmost importance to further improve electrocatalysts for electrochemical CO conversion. Here, we present a multiscale in situ investigation of activation and deactivation pathways of oxide-derived copper electrocatalysts under CO reduction conditions. Using well-defined CuO octahedra and cubes, in situ X-ray scattering experiments track morphological changes at small scattering angles and phase transformations at wide angles, with millisecond to second time resolution and ensemble-scale statistics. We find that undercoordinated active sites promote CO reduction products directly after CuO to Cu activation, whereas less active planar surface sites evolve over time. These multiscale insights highlight the dynamic and intimate relationship between electrocatalyst structure, surface-adsorbed molecules, and catalytic performance, and our in situ X-ray scattering methodology serves as an additional tool to elucidate the factors that govern electrocatalyst (de)stabilization.