We report mesoporous Mn_1.8Fe_1.2O₄ nanocubes that are synthesized through simple self-assembly and calcination. By changing the calcination temperature, we investigated the correlation between the nanostructure and catalytic performance of mesoporous Mn_1.8Fe_1.2O₄ catalysts. Mesoporous Mn_1.8Fe_1.2O₄ exhibited high oxygen evolution activity in both the photochemical and cerium (IV)-driven water oxidation systems. The highest initial turnover frequency (TOF) of 4.6 × 10⁻⁴ s⁻¹ per metal atom is obtained at neutral pH in photocatalytic water oxidation reaction, compared with those nonporous MnFe₂O₄, Fe₃O₄, and Mn₃O₄. In a cerium (IV)-driven environment, a high TOF of 1.8 × 10⁻³ s⁻¹ per metal atom is achieved, which is at least two orders of magnitude more active than that of nonporous MnFe₂O₄. Multiple experimental results (e.g., XRD, FT-IR, SEM, TEM, and XPS) confirmed that mesoporous Mn_1.8Fe_1.2O₄ materials are highly stable. Our results provide a facile method for synthesis of an inexpensive and highly active heterogeneous catalyst for the oxygen evolution reaction.