The configurations associated with reversible and irreversible adsorption of hydrogen on MgO escape consensus. Here, we report the dissociation of H2 on MgO nanocubes, which was examined by combining Fourier transform infrared spectroscopy and density functional theory (DFT)-based simulations. We found that the use of ultrahigh vacuum is essential for identifying the very first adsorption stages. Hydrogen pressure was varied from 10–8 mbar to near ambient, resulting in IR spectra of richer complexity than in current state of the art. Models with oxygen at regular corners (O3C) and Mg at inverse corners (MgIC) were identified to be the most reactive and to split H2 irreversibly already in the lowest pressure regime (PH2 < 10–3 mbar). The continuous increase in intensity of the corresponding IR bands (3712/1140 cm–1) in the intermediate range of pressures (10–3–1 mbar), along with the appearance of bands at 3605/1225 cm–1, was demonstrated to stem from cooperative adsorption mechanisms, which could be therefore considered as the main origin of irreversible hydrogen adsorption. At PH2 > 1 mbar, fully reversible adsorption was shown to occur at O4C (either on mono- or diatomic steps) and Mg3C sites. Another OH/MgH couple (3697/1030 cm–1) that became reinforced at high PH2 but remained stable upon pumping was correlated to O3C and MgIC in multiatomic steps. The difference in adsorption and desorption sequences confirmed the proposed cooperative adsorption of H2 molecules. Our study provides new insights into the mechanisms that can be beneficial for understanding the chemistry of H2 and other hydrogen-containing molecules, such as CH4, on oxide surfaces, but also for the advancement of hydrogen-storage technologies.