A challenge in actinide chemistry is activation of the strong bonds in the actinyl ions, AnO2+ and AnO22+, where An = U, Np, or Pu. Actinyl activation in oxo-exchange with water in solution is well established, but the exchange mechanisms are unknown. Gas-phase actinyl oxo-exchange is a means to probe these processes in detail for simple systems, which are amenable to computational modeling. Gas-phase exchange reactions of UO2+, NpO2+, PuO 2+, and UO22+ with water and methanol were studied by experiment and density functional theory (DFT); reported for the first time are experimental results for UO2 2+ and for methanol exchange, as well as exchange rate constants. Key findings are faster exchange of UO22+ versus UO 2+ and faster exchange with methanol versus water; faster exchange of UO2+ versus PuO2+ was quantified. Computed potential energy profiles (PEPs) are in accord with the observed kinetics, validating the utility of DFT to model these exchange processes. The seemingly enigmatic result of faster exchange for uranyl, which has the strongest oxo-bonds, may reflect reduced covalency in uranyl as compared with plutonyl.