The kinetic energy-dependent reactions of the atomic actinide uranium cation (U⁺) with H₂, D₂, and HD were examined by guided ion beam tandem mass spectrometry. An average 0 K bond dissociation energy of D₀(U⁺ - H) = 2.48 ± 0.06 eV is obtained by analysis of the endothermic product ion cross sections. Quantum chemistry calculations were performed for comparison with experimental thermochemistry, including high-level CASSCF-CASPT2-RASSI calculations of the spin-orbit corrections. CCSD(T) and the CASSCF levels show excellent agreement with experiment, whereas B3LYP and PBE0 slightly overestimate and the M06 approach badly underestimates the bond energy for UH⁺. Theory was also used to investigate the electronic structures of the reaction intermediates and potential energy surfaces. The experimental product branching ratio for the reaction of U⁺ with HD indicates that these reactions occur primarily via a direct reaction mechanism, despite the presence of a deep-well for UH₂⁺ formation according to theory. The reactivity and hydride bond energy for U⁺ are compared with those for transition metal, lanthanide, and actinide cations, and periodic trends are discussed. These comparisons suggest that the 5f electrons on uranium are largely core and uninvolved in the reactive chemistry.