The crystal structure of a novel Mg2Fe2O5 oxide synthetized at 15 GPa and 1550 °C has been determined by means of single-crystal X-ray diffraction. This compound is isostructural with Fe4O5 and can be considered as the other end-member of a solid solution between these two oxides involving the substitution of Fe2+ for Mg. The resulting unit-cell lattice parameters a = 2.8889(4), b = 9.7282(4), and c = 12.5523(7) Å are smaller than those of Fe4O5. Mg and Fe3+ cations are found to be disordered among the three crystallographic sites of the Mg2Fe2O5 structure, although preference of Mg for the trigonal prism coordination (M3) is observed. Substitution of Mg into the Fe4O5 structure reduces the octahedral distortion of both the M1 and M2 sites. Like Mg, Cr has recently been found to substitute into Fe4O5, so that Fe3+/∑Fe can vary from 0 to 1.0 in the Mg-Cr-Fe oxides system. Substitution of both Mg and Cr in Fe4O5 also makes this phase more relevant for bulk compositions expected in the Earth’s transition zone and deep upper mantle. M4O5 phases having the CaFe3O5-type structure, therefore, need to be considered as a new addition to the phase relations of several simple oxide systems at pressure and temperature conditions at which the spinel-structured phases become unstable.