Wheel polygon amplitude can greatly affect wheel-rail vibration and sound radiation. Based on multi-body dynamics theory, a vehicle-track rigid-flexible coupling dynamics model was established. According to the actual running wear condition of the wheel, the wheel-rail vibration response was calculated and analyzed (the order of wheel polygons is 20, and the polygon amplitude is 0.01/0.02/0.03/0.04 mm, respectively). Together with the finite element/boundary model of the wheel, the calculated wheel-rail force was used as an external incentive to analyze the effects of polygon amplitude on the time-frequency domain of wheel noise. The research results show that: when the polygon order is 20, with the increase of polygon amplitude, the wheel-rail vertical force and the acceleration of wheel, rail and track slab increase gradually. It’s also found that the rail acceleration is obviously more sensitive to the amplitude than the track slab acceleration, while the vertical displacement of the rail and track slab is less sensitive to the polygon amplitude. At the same amplitude, the closer to the wheel rolling line, the more obvious the sound pressure decreases with the increase of height. At different amplitudes, the sound pressure at different positions will increase with the rise of the polygon amplitude. The root mean square value of sound power increases gradually with the addition of amplitude: When the amplitude changes from 0.01 mm to 0.04 mm, the calculated sound power increases by 4.1 dB.