A fundamental study on the metal−support interactions of supported metal catalysts is of great importance for developing heterogeneous catalysts with high performance, is still attracting and challenging in many heterogeneous catalytic reactions. In this work, we report the catalytic performances of CeO 2 -supported noble-metal catalysts among single atoms, subnanoclusters (∼1 nm), and nanoparticles (2.2−2.7 nm) upon low-temperature CO oxidation reaction between 50 and 250 °C. The subnanoclusters and nanoparticles of Ru, Rh, and Ir showed much higher activities than those of the single atoms, while a Pd single-atom catalyst was more active than Pd subnanoclusters and nanoparticles. According to the results of multiple ex situ and in situ characterizations, the much different activities of Ru, Rh, Ir, and Pd were derived from the alterable electronic metal−support interactions (EMSI), which determine the concurrent reaction pathway including the famous Mars van Krevelen mechanism and carbonate−intermediate route on the most active metal sites of M δ+ (0 < δ < 1) for Ru, Rh, and Ir and Pd 2+ for Pd. Also, the moderate EMSI of CeO 2 -supported Rh subnanoclusters furthest benefited activation of the adsorbed CO molecule and ensured it the highest activity among CeO 2 -supported Ru, Rh, and Ir catalysts with similar metal deposit sizes.