The compressibility and structural behavior of the novel Mg2Fe2O5 oxide has been investigated by in situ single-crystal X-ray diffraction in a diamond-anvil cell up to a pressure of 17 GPa. The bulk compressibility of Mg2Fe2O5 can be described using a second-order Birch-Murnaghan equation of state (BM2 EoS) with V0 = 352.4(2) Å3 and K0 = 171(4) GPa. Three linear BM2 EoS were used to describe the axial compressibility of Mg2Fe2O5, which was found to be highly anisotropic. The a and b lattice parameters have very similar compressibilies, with a0 = 2.8917(11) Å and linear modulus Ma = 572(16) GPa and b0 = 9.736(3) Å and linear modulus Mb = 583(15) GPa, respectively. The c-axis is the most compressible direction as indicated by the smaller linear modulus [c0 = 12.520(15) Å and Mc = 404(28) GPa]. The Mg2Fe2O5 structure consists of edge-sharing octahedra alternating with layers of trigonal prisms. The compression behavior of the M-O bonds of the M1 and M2 octahedra and of the M3 prisms depend on their location in either an edge-sharing environment, which makes them stiffer, or a corner-sharing environment where they have more freedom to distort and compress. The main compression mechanism consists of a polyhedral tilting around the M2-O1-M2 angle, which decreases with increasing pressure. Mg2Fe2O5 has recently been added to the list of stable end-members of phases with M4O5 stoichiometry, making it a potentially relevant phase in the Earth’s upper mantle and transition zone. To develop thermodynamic activity-composition models for high-pressure phases, it is crucial to know the accurate elastic parameters of each individual end-member. Currently these have only been measured for Mg2Fe2O5 (this study) and Fe4O5.