The single gold atom doped aluminum oxide clusters AuAl3O3+, AuAl3O4+, and AuAl3O5+ have been prepared and mass-selected to react with CO, O-2, and mixtures of CO and O2 in an ion trap reactor under thermal collision conditions. The reactions have been characterized by mass spectrometry with isotopic substitution (O-16(2) -> O-18(2)) and density functional theory calculations. The AuAl3O5+ cluster can oxidize two CO molecules consecutively to form AuAl3O4+ and then AuAl3O3+, the latter of which can react with one O-2 molecule to regenerate AuAl3O5+. The (AuAl3O3+)-O-16 ions interact with a mixture of (CO)-O-16 and O-18(2) to produce the fully substituted O-18 species (AuAl3O3-5+)-O-18, which firmly identifies a catalytic cycle for CO oxidation by O-2. The oxidation catalysis is driven by electron cycling primarily through making and breaking a goldaluminum chemical bond. To the best of our knowledge, this is the first identification of catalytic CO oxidation by O-2 mediated with gas-phase cluster catalysts with single-noble-metal atoms, which serves as an important step to understand single-atom catalysis at strictly a molecular level.