<p>Axle box bearings are critical components of high-speed trains. Localized defects, such as pitting and spalling, on raceways or rollers pose significant threats to the operational safety of railway vehicles. In this work, a novel bearing-flexible axle box-vehicle coupling model is established to explore the vibration characteristics of axle box bearings with irregular localized defects. First, based on the contact and kinematic relationship between rollers and raceways, the three-dimensional (3D) bearing force elements are analyzed and formulated. Second, the established model and a flexible axle box are integrated into the vehicle, and the responses of the normal and faulty bearings under the combined excitations of wheel roughness and track irregularities are simulated. Third, the simulation results are verified through a rolling-vibrating test bench for full-scale wheelsets of high-speed trains. The comparisons of the fault-induced repetitive transients in the time-domain and the fault characteristic frequencies in the envelope spectra demonstrate the efficiency of the proposed model. Finally, based on the flexible axle box model, a sensitivity analysis of the accelerometer placements to the bearing faults is carried out, and the optimal one is identified based on both the time-domain and frequency-domain signal-to-noise ratios (SNRs) for engineering applications.</p>