Railway wheel polygonization is a type of uneven wear of material which worsens the running stability of trains. As a significant factor influencing the wear, wheel-rail hardness matching (i.e., the hardness ratio HW/HR) might affect the formation of a polygonal wheel. Thus, rolling-sliding wear tests were conducted using three wheel steels matching two rail steels to explore the influence of HW/HR (ranging from 0.649 to 1.263) on the initiation and evolution of wheel polygonal wear. The results show that when matching the softer rail, the wheel was less likely to become polygonal with an increase in HW/HR. When matching the harder rail, the wheel presented earlier polygon initiation under a moderate HW/HR of 0.792. The largest HW/HR of 1.263 presented the best anti-polygon condition for wheel material. The wear mechanism of polygonal wheel was dominated by abrasive, fatigue and oxidative wear at the crest and fatigue wear at the trough.