Abstract: In order to reveal the fatigue damage mechanism of the electron beam welding joint of superalloy and predict its life accurately, the simulation method for fatigue crack initiation in the welding joint was studied. The cyclic hysteretic energy model was combined with the continuum damage mechanics theory to establish the damage parameters, and the numerical simulation method of fatigue crack initiation was established by secondary development of advanced simulation for engineering and sciences Abaqus using Python language. Based on the results of metallographic tests, the microstructure geometry model of the GH4169 electron beam welding joint was established by using the improved Voronoi diagram method, and the multi-slip band model was generated. Based on the above method, the fatigue crack initiation simulation under different strain amplitudes of the electron beam welding joint were put in practice. The results have shown that the fatigue cracks all initiate in heat heat-affected zone (HAZ) of the joints. The number of cycles when the crack reaches 500 µm is defined as the crack initiation life. As the strain amplitude increases, the crack initiation life gradually decreases, and the predicted life in simulation was in good agreement with the experimental data. The test and simulation of notched part fatigue were carried out. The results have shown that the simulated fatigue crack initiation location, micro propagation, and connection law fit with the experimental results, which further verifies the validity of the proposed method.