The performance of supported metal catalysts can depend on many factors, including metal particle size and dispersion and metal–support interactions, and differentiation of these effects is challenging because of their interwoven relationship. Copper/ceria catalysts are well-known redox catalysts studied in the conversion of CO and CO2 via oxidation and/or reduction pathways. The redox behaviors of each species, Cu-CuO and CeO x -CeO2, are often suggested to be interlinked, allowing ceria-supported copper domains to outperform copper species on other, nonredox active supports. In this work, the catalytic activity of nanosized Cu supported on either cerium oxide or mesoporous silica is explored using samples where the Cu weight loading, particle size, and dispersion of Cu are held constant to highlight the impact of the two supports on catalytic performance without additional influencing factors. The Cu/CeO2 catalysts are synthesized via a space-confined method to limit the growth of CeO2 particles and to achieve a high dispersion of Cu. Through in situ XRD and XAS, it is shown that the presence of Cu nanoparticles on the CeO2 support lowers the reduction temperature of CeO2, allowing formation of oxygen vacancies at low temperatures <300 °C. The Cu/CeO x catalyst demonstrates 100% CO selectivity in the low temperature (300 °C) and ambient pressure conversion of CO2 to CO, even when approaching equilibrium conversion. Moreover, this catalyst is approximately 4 times more active than the corresponding Cu/SiO2 catalyst with otherwise similar structural attributes. The potential reaction pathways are probed by in situ FTIR and in situ XAS at various temperatures, identifying Cu+-CO species and oxygen vacancies forming under some conditions. The collected experimental evidence also suggests a reaction sequence for CO2 hydrogenation over Cu/CeO x catalysts, consistent with DFT reports in the literature.