Wear is an important factor that determines the normal functioning of high-speed transmission. This study aimed to analyze the stress distribution of high-speed transmission using finite element software and the principle of wear reliability. The weak parts where the stress was concentrated were identified. Tests were performed under different conditions using a uniform design. Thus, the major factors influencing the wear prediction model were identified as surface hardness of material, load, and sliding velocity. A mathematical model for wear prediction was then established using the partial least squares method. Experimental verification was performed, and the high precision of the prediction model was confirmed.