Rail wear is one of the main reasons for reducing the service life of high-speed railway turnouts in China. The rail wear characteristics of high-speed railway turnouts are influenced by a large number of input parameters of the complex train-turnout system. To reproduce the actual operation conditions of railway turnouts, random distributions of these inputs need to be considered in rail wear simulation. For a given nominal layout of the high-speed railway turnout, 19 input parameters for rail wear simulation in high-speed railway turnouts are investigated based on orthogonal design of experiment. Three dynamic responses (wheel−rail friction work, normal contact force and size of contact patch) are defined as observed values and the significant factors (direction of passage, axle load, running speed, friction coefficient, and wheel and rail profiles) are determined by two unreplicated saturated factorial design methods, including the half-normal probability plot method and Dong93 method. As part of the associated rail wear simulation, the influence of the wear models and the local elastic deformation on the rail wear was separately investigated. The calculation results for the wear models are quite different, especially for large creep mode. The local elastic deformation has a large effect on the sliding speed and rail wear and needs to be considered in the rail wear simulation.