Aiming at the problem of coaxial wheel partial wear of HX high-power electric locomotive in China, the locomotive dynamics model was established based on the dynamics software SIMPACK, and the damage function prediction method based on wear number was used to analyze the influence of different coaxial sequence, wheel diameter difference, curve radius and other conditions on wheel tread damage. The results show that when there is wheel diameter difference in one axle or multiple axles, the influence on tread damage of 2-axle and 3-axle wheels is greater, and the influence on 1-axle wheels is less. For different values of wheel diameter difference, with the increase of wheel diameter difference, the impact of rolling contact fatigue degree on the right wheel tread of 1-axle is small, and the wear degree of the left wheel tread increases. The damage degree of wheel on both sides of 2-axle is reduced; the cracks of 3-axle left wheel are accentuated. Under left curve condition and R400 condition, wheel diameter difference has greater influence on the wear and rolling contact fatigue of each axle. Under right curve condition and R800 condition, wheel diameter difference has more influence on the wear and rolling contact fatigue of each axle. Compared with right curve condition, wheel diameter difference has more influence on wheel tread damage under left curve condition. Compared with curve radius, wheel diameter difference has less influence on wheel tread damage.