This paper deals with the fatigue damage of the welded cantilever under a high-speed train subjected to wind-induced loading using a field test campaign and a CFD (Computational Fluid Dynamic) simulation. The results show that significant airflow pressure on the cantilever frames and the structural resonance are the main cause of the fatigue damage of welded joints. During long-term operation, the free end of the cantilever tends to vibrate undesirably, which affects the service life of the structure. Firstly, a finite element model with constant amplitude of wind pressure is created based on the current design specifications to assess the static and fatigue strength of the cantilever. The simulation results show that the structural strength meets the standard design requirements. However, the results of the field test show that the acceleration at the free end of the cantilever is 32.0 m/s2, which far exceeds the relevant requirements. Meanwhile, there is a significant difference in aerodynamic pressure on the frame surfaces between the leading and trailing cars. An aerodynamic model is created for two full-size cars with the CFD method. The results show that FIV (flow-induced vibration) is the main cause of the continuous vibration of the elastic cantilever frame as long as the wake shedding occurs at a frequency close to the natural frequency of the frame. This study provides a reference for the aerodynamic fatigue design of the equipment mounted high-speed trains, especially for structures with low stiffness affected by open airflow.