In order to investigate the fatigue crack growth process of steel orthotropic bridge deck, and provide theoretical guidance for the anti-fatigue design and reinforcement, the real bridge’s finite model based numerical simulation method and process of the fatigue crack growth of steel orthotropic bridge deck was proposed. Firstly, the critical locations that are apt to suffer fatigue failure of the whole bridge are ascertained by the field survey results and the analysis of the whole structure under the dead load and the live load. Then, the refined finite element model with typical welded details for the locations is established to analyze the stress amplitude. According to the vehicle-bridge vibration based analysis method, the influence of the stress impact factor on the stress amplitude is taken into account. Determine the fatigue crack propagation direction, path, and fatigue life, and then analysis the total process of fatigue crack propagation. Finally, take the fatigue crack propagation analysis of an existing long-span cable stayed bridge with steel orthotropic bridge deck as example, which indicates the feasibility and accuracy of the method and calculation process, and provides a theoretical basis for the bridge fatigue failure repair and reinforcement in operation period.