This study focuses on the variation in activity-controlling factors during CO catalytic ignition over a CuO–CeO2 catalyst. The activity for CO combustion follows the decreasing order of CuO–CeO2 > CuO > CeO2. Except for inactive CeO2, increasing temperature induces CO ignition to achieve self-sustained combustion over CuO and CuO–CeO2. However, CuO provides enough copper sites to adsorb CO, and abundant active lattice oxygen, thus obtaining a higher hot zone temperature (208.3°C) than that of CuO–CeO2 (197.3 °C). Catalytic ignition triggers a kinetic transition from the low-rate steady-state regime to a high-rate steady-state regime. During the induction process, Raman, X-ray photoelectron spectroscopy (XPS), CO temperature-programmed desorption (CO-TPD) and infrared (IR) spectroscopy results suggested that CO is preferentially adsorbed on oxygen vacancies (Cu+-[Ov]-Ce3+) to yield Cu+-[CO]-Ce3+ complexes. Because of the self-poisoning of CO, the adsorbed CO and traces of adsorbed oxygen react at a relative rate, which is entirely governed by the kinetics on the CO-covered surface and the heat transport until the pre-ignition regime. Nonetheless, the Cu+-[CO]-Ce3+ complex is a major contributor to CO ignition. The step-response runs and kinetic models testified that after ignition, a kinetic phase transition occurs from a CO-covered surface to an active lattice oxygen-covered surface. During CO self-sustained combustion, the rapid gas diffusivity and mass transfer is beneficial for handling the low coverage of CO. The active lattice oxygen of CuO takes part in CO oxidation.