Two types of high power alternating current (AC) locomotive in China are prone to serious high-order polygonal wear, which has significant negative effects on the operation of locomotives. This study investigates factors influencing polygonal wear in locomotive wheels and determines methods of minimizing operation damage. We designed experiments to analyze the process of polygonization formation of wheels to identify the key influencing factors, finding that natural vibration of wheelsets is the central inherent factor of wheel polygonization and that these vibrations can be easily stimulated by wheel or rail irregularities. We found that poor re-profiling quality is the key external factor in these irregularities. The wheelset bending resonance is activated when the remaining wheel polygonal wear has a wavelength of 200 mm in the 1/3 octave band, in turn leading to significant increases of wheel polygonal wear. In this study, we review a new wheelset design that can mitigate and/or eliminate the polygonal wheel wear due to increased stiffness in wheel bending. We evaluate the potential capacity of the newly designed wheelset and propose two proven effective measures to further improve the wheel re-profiling quality for polygonal wear.