The high cycle fatigue (HCF) and very high cycle fatigue (VHCF) behaviors of medium carbon pearlitic wheel steels were investigated by the combination of conventional tension-compression fatigue test (up to 108 cycles, frequency of 150 Hz) and ultrasonic fatigue test (up to 109 cycles, frequency of 20 kHz). In the S-N curves, fatigue limit plateaus were found in the range of 107–108 cycles for the conventional fatigue test and in the range of 108–109 cycles for the ultrasonic fatigue test. No fatigue failures were found in the VHCF regime. The fatigue fractures were mainly originated from the surface matrix of specimens, and a small amount of fracture origins were the surface/subsurface inclusions or internal inclusions. Only oxide inclusions were found to cause fatigue fracture, while crack initiation was not found to be associated with sulfides in this work. The effects of pearlite block size and inclusion size on the fatigue strength were discussed based on the Murakami model. The fatigue limit was slightly improved by the grain size refinement, but was insensitive to inclusions. The main reason was that the sizes of most inclusions in the tested steels were smaller than the critical size, below which fatigue failure can hardly occur from inclusions. When most of the oxides were enveloped in sulfides, the fatigue properties, however, were not obviously improved. This is because the sizes of those oxides encapsulated by sulfides were substantially smaller than the critical inclusion size, while large-sized oxides were not found to be encapsulated by sulfides. Compared to the conventional high strength steels with the tensile strength beyond 1200 MPa, the lower sensitivity of fatigue behavior to inclusions was found in the studied steels, mainly due to the larger critical inclusion sizes.