<p>This study systematically investigates the influence of Mn element on the stability and anisotropic behavior of the Al₈Mn₅ phase in AZ80 magnesium alloy by combining first-principles calculations, thermodynamic simulations, and experimental validation. The microstructure evolution was further verified using JMatPro phase diagram simulations and metallographic experiments. The results indicate that the Al₈Mn₅ phase possesses high structural stability and toughness (B/G=1.76). Furthermore, this phase exhibits significant anisotropy in elastic modulus, shear modulus, and strain energy density. Experimental studies show that with increasing Mn content (0.15~0.35 wt.%), the precipitation amount of the Al₈Mn₅ phase in the alloy increases. Its dispersed distribution effectively refines the grains, reducing the grain size from 215 to 96 μm, and suppresses the formation of the network-like β-Mg₁₇Al₁₂ phase. This research elucidates the stability and toughening essence of the Al₈Mn₅ phase from the atomic–electronic scale and verifies its role in microstructure regulation through macroscopic experiments, providing a solid theoretical and experimental basis for optimizing the comprehensive properties of AZ80 alloy through Mn microalloying.</p>