Mechanistic insight into the thermal O-H bond activation of water by the cubane-like, prototypical heteronuclear oxide cluster [Al2Mg2O5](center dot+) has been derived from a combined experimental/computational study. Experiments in the highly diluted gas phase using Fourier transform ion cyclotron resonance mass spectrometry show that hydrogen-atom abstraction from water by the cluster cation [Al2Mg2O5](center dot+) occurs at ambient conditions accompanied by the liberation of an OH center dot radical. Because of a complete randomization of all oxygen atoms prior to fragmentation, about 83% of the oxygen atoms of the hydroxyl radical released originate from the oxide cluster itself. The experimental findings are supported by detailed high-level quantum chemical calculations. The theoretical analysis reveals that the transfer of a formal hydrogen atom from water to the metal-oxide cation can proceed mechanistically via proton- or hydrogen-atom transfer exploiting different active sites of the cluster oxide. In addition to the unprecedented oxygen-atom scrambling, one of the more general and quite unexpected findings concerns the role of spin density at the hydrogen-acceptor oxide atom. While this feature is crucial for [M-O](+)/CH4 couples, it is much less important in the O-H bond activation of water.