Single‐atom catalysts are a fast‐emerging area in which late‐transition metal atoms are supported on oxides, metals, and carbonaceous supports. They show great promise for selective chemical reactions due to their well‐defined active sites, and significantly reduce precious metal loading. However, oxide‐supported single‐atom catalysts have drawbacks such as deactivation due to sintering, and there are on‐going debates about the exact nature of the active sites. Herein we report a model system where the surface temperature during Rh deposition on a copper oxide support dictates the Rh size distribution. Our temperature‐programmed desorption experiments reveal that Rh clusters perform CO oxidation at lower temperature than single atoms, and isotopic labelling demonstrates differences in the mechanism in that the C−O bond is broken and reformed on clusters, as opposed to a pure Mars van Krevelen mechanism for CO oxidation at the single‐atom Rh sites. We further examine the cluster size distributions with scanning tunneling microscopy and X‐ray photoelectron spectroscopy which confirm the presence of both clusters and single atoms for the lower temperature deposition and only single atoms for the higher temperature deposition. Together, these results provide a fundamental understanding of the differences in the CO oxidation mechanism on Rh atoms and clusters.