Phase segregation in hydride-forming alloys may persist under the action of multiple hydrogenation/dehydrogenation cycles. We use this effect to destabilize metal hydrides in the immiscible Mg-Mn system. Here, in the MgxMn1-x thin films, the Mg and Mn domains are chemically segregated at the nanoscale. In Mn-rich compositions, the desorption pressure of hydrogen from MgH2 is elevated at a given temperature, indicating a thermodynamic destabilization. The increase in the desorption pressure of hydrogen reaches ∼2.5 orders in magnitude for x = 0.30 at moderate temperatures. Such large thermodynamic destabilization allows the MgH2 to reversibly absorb and desorb hydrogen even at room temperature. Our strategy to use immiscible elements for destabilization of MgH2 is effective and opens up the possibility for the development of advanced and low-cost hydrogen storage and supply systems.