The effects of pressure and temperature on the reactivities of niobium cluster cations Nbn+(n=4–16) toward molecular hydrogen and H2/D2 mixture were studied using a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer combined with a laser-ablation/supersonic-jet external ion source. It was shown that the rate constants of the reactions of most Nbn+ clusters with the first H2 molecule exhibit pronounced fall-off behavior in the total pressure range of 10−6–10−4 Torr. For the Nbn++H2/D2 reactions, the H/D scrambling in the reaction products and the apparent kinetic isotope effects were also found to be strongly pressure-dependent. The observed phenomena are consistent with a reaction mechanism that involves a sequence of reversible stages of dissociative chemisorption of H2 (or D2) molecules on Nbn+ clusters. The fall-off effects can explain the apparent negative temperature dependence for the Nbn++H2 reaction rate constants, the difference between the kinetic data obtained in FT-ICR and fast-flow reactor studies, and the observed enhanced kinetic isotope effects. Indirect evidence was obtained showing that the low reactivities of certain Nbn+ clusters (n=8, 10, and 16) toward hydrogen are due to activation barriers rather than low chemisorption energies.