The heteronuclear metal oxide complexes are of great significance in heterogeneous catalytic oxidation of CO. However, previous studies are mainly focused on the composition of metal oxide, charge state, the support and the active oxygen species, with little attention paid to adsorbed CO ligands. Herein, the ligand-mediated reactivity in CO oxidation of niobium-nickel monoxide carbonyl complexes has been successfully identified. The NbNiO(CO) n- ( n = 5-6) anions are determined to be O-bridged complexes. In contrast, the NbNiO(CO) n- ( n = 7-8) anions are characterized to be η2-CO2-tagged complexes. The crucial roles of the multiply adsorbed CO molecules that can facilitate not only the competitive binding with bridging oxygen atom to the transition metal centers but also the electron accumulation of transition metal atoms have been discovered. The fascinating results are of substantial importance to understand the mechanisms of CO oxidation over heteronuclear metal oxide under CO-rich feed condition.