8Cr4Mo4V, as an ideal choice for aeroengines bearing materials, involves multi-scale damage mechanisms of the fatigue crack failures. Herein, we propose a multi-scale analysis method to analyze the crack initiation and propagation damage mechanisms of 8Cr4Mo4V alloy. We find that different crystal orientations produce distinctly different damage mechanisms. The second phase doping also has different strengthening effects on the matrix following bypass and cut-through mechanisms. Meanwhile, the study of the polycrystalline model verified the micro-scale inverse Hall-Petch relation, where material strength decreases with grain refinement. Phase transitions caused by dislocations lead to stress concentration at specific grain boundaries, becoming the main inducer for the nucleation of initial voids. To address micro-to-macroscale-crossing issues, we constructed a large-scale mesoscopic molecular dynamics simulation and proposed an analytical formula to predict the relationship between average grain size and yield stress. Finally, we combine macroscopic experiments, crystallographic analyses, and atomic-scale characterization, verifying the combined action of dislocations and stacking faults leads to the failure of the material.