CO elimination through oxidation over highly active and cost-effective catalysts is a way forward for many processes of industrial and environmental importance. In this study, doped CeO₂ with transition metals (TM = Cu, Co, Mn, Fe, Ni, Zr, and Zn) at a level of 20 at. % was tested for CO oxidation. The oxides were prepared using microwave-assisted sol–gel synthesis to improve catalyst’s performance for the reaction of interest. The effect of heteroatoms on the physicochemical properties (structure, morphology, porosity, and reducibility) of the binary oxides M–Ce–O was meticulously investigated and correlated to their CO oxidation activity. It was found that the catalytic activity (per gram basis or TOF, s^–1) follows the order Cu–Ce–O > Ce–Co–O > Ni–Ce–O > Mn–Ce–O > Fe–Ce–O > Ce–Zn–O > CeO₂. Participation of mobile lattice oxygen species in the CO/O₂ reaction does occur, the extent of which is heteroatom-dependent. For that, state-of-the-art transient isotopic ¹⁸O-labeled experiments involving ¹⁶O/¹⁸O exchange followed by step-gas CO/Ar or CO/O₂/Ar switches were used to quantify the contribution of lattice oxygen to the reaction. SSITKA-DRIFTS studies probed the formation of carbonates while validating the Mars–van Krevelen (MvK) mechanism. Scanning transmission electron microscopy-high-angle annular dark field imaging coupled with energy-dispersive spectroscopy proved that the elemental composition of dopants in the individual nanoparticle of ceria is less than their composition at a larger scale, allowing the assessment of the doping efficacy. Despite the similar structural features of the catalysts, a clear difference in the O_lattice mobility was also found as well as its participation (as expressed with the α descriptor) in the reaction, following the order α_Cu > α_Co> α_Mn > α_Zn. Kinetic studies showed that it is rather the pre-exponential (entropic) factor and not the lowering of activation energy that justifies the order of activity of the solids. DFT calculations showed that the adsorption of CO on the Cu-doped CeO₂ surface is more favorable (−16.63 eV), followed by Co, Mn, Zn (−14.46, −4.90, and −4.24 eV, respectively), and pure CeO₂ (−0.63 eV). Also, copper compensates almost three times more charge (0.37e⁻) compared to Co and Mn, ca. 0.13e⁻ and 0.10e⁻, respectively, corroborating for its tendency to be reduced. Surface analysis (X-ray photoelectron spectroscopy), apart from the oxidation state of the elements, revealed a heteroatom–ceria surface interaction (O_a species) of different extents and of different populations of O_a species.