As a common condition in train operation, the out-of-roundness (OOR) of wheels may have a great influence on the life of cracked wheels. In this study, the I-II mixed-mode crack growth rate of different angles was tested, finite element analysis was carried out by using the test results, and the influence of different wheel roundness conditions on the life of cracked wheels was revealed. The results show that the mode II stress intensity factor of mixed-mode cracks is the main driving force for crack propagation in the process of wheel rim crack growth. With an increase in the wheel scar length and the order of the wheel polygon, the crack propagation life decreases significantly.