A customized reflection time-of-flight (Re-TOF) mass spectrometer combined with a 177 nm deep-ultraviolet laser has enabled us to observe well-resolved cobalt clusters Co-n(+/-/0) and perform a comprehensive study of their reactivity with ammonia (NH3). The anions Co-n(-) are found to be inert, the neutrals allow the adsorption of multiple NH3 molecules, while the cationic Co-n(+) clusters readily react with NH3 giving rise to dehydrogenation. However, incidental dehydrogenation of NH3 on Co-n(+) is only observed for n = 3. The dramatic charge- and size-dependent reactivities of Co-n(+/-/0) clusters with NH3 are studied by the density functional theory (DFT)-calculation results of energetics, density of states, orbital interactions, and reaction dynamics. We illustrate the dehydrogenation from two NH3 molecules, where a significantly reduced transition-state energy barrier is found pertaining to the dimolecular co-catalysis effect. The reactivity of Co-3(+) with NH3 is illustrated showing effective catalysis for N-H dissociation to produce hydrogen applicable for designing ammonia fuel cells.