Gas-phase reactivity of the copper hydride anions [CuH2](-) and [Cu2H3](-) toward a range of neutral reagents has been examined via multistage mass spectrometry experiments in a linear ion trap. mass spectrometer in conjunction with isotope labeling studies and Density Functional Theory (DFT) calculations. [CuH2](-) is more reactive than [Cu2H3](-), consistent with DFT calculations, which show it has a higher energy HOMO. Experimentally, [CuH2](-) was found to react with CS2 via hydride transfer to give thioformate (HCS2-) in competition with the formation of the organometallic [CuCS2](-) ion via liberation of hydrogen; CO2 via insertion to produce [HCuO2CH](-); methyl iodide and allyl iodide to give I- and [CuHI](-); and 2,2,2-trifluoroethanol and 1-butanethiol via protonation to give hydrogen and the product anions [CuH(OCH2CF3)](-) and [CuH(SBu)](-). In contrast, the weaker acid methanol was found to be unreactive. DFT calculations reveal that the differences in reactivity between CS2 and CO2 are due to the lower lying pi* orbital of the former, which allows it to accept electron density from the Cu center to form the initial three-membered ring complex intermediate, [H2Cu(eta(2)-CS2)](-). In contrast, CO2 undergoes the barrierless side-on hydride transfer promoted by the high electronegativity of the oxygen atoms. Side-on dS(N)2 mechanisms for reactions of [CuH2](-) with methyl iodide and allyl iodide are favored on the basis of DFT calculations. Finally, the DFT calculated barriers for protonation of [CuH2](-) by methanol, 2,2,2-trifluoroethanol, and 1-butanethiol correlate with their gas-phase acidities, suggesting that reactivity is mainly controlled by the acidity of the substrate.