The aromatic properties of lignin make it a promising source of valuable chemicals and fuels. Developing efficient and stable catalysts to effectively convert lignin into high-value chemicals is challenging. In this work, MnFe₂O₄ spinel catalysts with oxygen-rich vacancies and porous distribution were synthesized by a simple solvothermal process and used to catalyze the depolymerization of lignin in an isopropanol solvent system. The specific surface area was 110.5 m²∙g^–1, which substantially increased the active sites for lignin depolymerization compared to Fe₃O₄. The conversion of lignin reached 94%, and the selectivity of alkylphenols exceeded 90% after 5 h at 250 °C. Underpinned by characterizations, products, and density functional theory analysis, the results showed that the catalytic performance of MnFe₂O₄ was attributed to the composition of Mn and Fe with strong Mn–O–Fe synergy. In addition, the cycling experiments and characterization showed that the depolymerized lignin on MnFe₂O₄ has excellent cycling stability. Thus, our work provides valuable insights into the mechanism of lignin catalytic depolymerization and paves the way for the industrial-scale application of this process.