Laser ablation generated Au-x(TiO2)(y)O-z(-) (x = 0, 1; y = 2, 3; z = 1, 2) oxide cluster anions have been mass-selected using a quadrupole mass filter and reacted with CO in a hexapole collision cell. The reactions have been characterized by time-of-flight mass spectrometry and density functional theory calculations. Gold-titanium bimetallic oxide clusters Au(TiO2)(y)O-z(-) are more reactive in CO oxidation than pure titanium oxide clusters (TiO2)(y)O-z(-). The computational studies identify the dual roles that the gold atom plays in CO oxidation: functioning as a CO trapper and electron acceptor. Both factors are important for the high reactivity of Au(TiO2)(y)O-z(-) clusters. To the best of our knowledge, this is the first example of CO oxidation by gold-containing heteronuclear oxide clusters, which provides molecular-level insights into the roles of gold in CO oxidation over oxide supports.