Wind-induced response poses a significant challenge to the stability of extra-large-span heavy steel box girders during synchronous lifting operations. This study adopted a method combining numerical simulation with on-site monitoring to investigate the aerodynamic characteristics the beam during the overall hoisting process of the Xiaotun Bridge. A high-fidelity finite element model was established using Midas NFX 2024 R1, and fluid–structure interaction (FSI) analysis was conducted, utilizing the RANS k-ε turbulence model to simulate stochastic wind fields. The results show that during the lifting stage from 3 m to 25 m, the maximum horizontal displacement of the steel box girder rapidly increases at wind angles of 90° and 60°, and the peak displacement is reached at 25 m. Under a strong breeze at a 90° wind angle and 25 m lifting height, the maximum lateral displacement was 42.88 mm based on FSI analysis, which is approximately 50% higher than the 28.58 mm obtained from linear static analysis. Subsequently, during the 25 m to 45 m lifting stage, the displacement gradually decreases and exhibits a linear correlation with lifting height. Concurrently, the maximum stress of the lifting lug of the steel box girder increases rapidly in the 3–25 m lifting stage, reaches the maximum at 25 m, and gradually stabilizes in the 25–45 m lifting stage. The lug stress under the same critical condition reached 190.80 MPa in FSI analysis, compared with 123.83 MPa in static analysis, highlighting a significant dynamic amplification. Furthermore, the detrimental coupling effect between mechanical vibrations from the lifting platform and wind loads was quantified; the anti-overturning stability coefficient was reduced by 10.48% under longitudinal vibration compared with lateral vibration, and a further reduction of up to 39.33% was caused by their synergy with wind excitation. Field monitoring validated the numerical model, with stress discrepancies below 9.7%. Based on these findings, a critical on-site wind speed threshold of 9.38 m/s was proposed, and integrated control methods were implemented to ensure construction safety. During on-site lifting, lifting lug stresses were monitored in real time, and if the predefined threshold was exceeded, contingency measures were immediately activated to ensure a controlled termination.