The thermal gas-phase reactions of Nb₂BN₂⁻ cluster anions with carbon dioxide have been explored by using the art of time-of-flight mass spectrometry and density functional theory calculations. Four CO₂ molecules can be consecutively reduced by Nb₂BN₂⁻, resulting in the formation of Nb₂BN₂O_1–4⁻ anions and the release of one CO molecule each time. To illustrate the role of ligands in Nb₂BN₂⁻, the reactivities of Nb₂N₂⁻ and Nb₂B⁻ toward CO₂ were also investigated; two and three CO₂ molecules are activated, respectively, and the rate constants are slower than that of Nb₂BN₂⁻/CO₂ systems. This comparison indicates that metal–metal multiple bonds and appropriate ligands, such as B, are important factors for CO₂ reduction. The synergy between a transition metal atom (Nb) and a main-group atom (B) in CO₂ reduction mediated by gas-phase clusters is revealed for the first time. To the best of our knowledge, Nb₂BN₂⁻ anions are gas-phase clusters that reduce the largest number of CO₂ molecules. A fundamental understanding of the efficient reduction of carbon dioxide molecules may shed light on the rational design of active sites on supported transition metal/boron nitride catalysts.