With the exception of [Cu(OH)]+, the thermal reactions of the first-row transition-metal hydroxide cations, [Sc(OH)]+–[Zn(OH)]+, with ammonia have been studied by means of gas-phase experiments and by computational methods for the whole series. The primary reaction channels involve NH bond activation, forming [M(NH2)]+ concomitantly with the elimination of water, and adduct formation, leading to [M(OH)(NH3)]+. Furthermore, [Ti(OH)]+ and [V(OH)]+ react with ammonia under dehydrogenation conditions, leading to [M,O,N,H2]+ (M=Ti, V), and for [Ni(OH)]+ ligand exchange is observed. Computations of the main reaction channels have been performed for the [M(OH)]+/NH3 couples (M=Sc–Zn) to uncover the underlying reaction mechanism and periodic trends across the first row. For NH bond activation, σ-bond metathesis was found to be the underlying mechanism.