Two 2.2Cr heat resistant steel samples that had been fatigue tested respectively at 550 °C and 650 °C are analyzed on the atomic scale to reveal the different crack initiation mechanisms. Cracks formed along prior austenite grain boundaries (PAGBs) are selected and manufactured into foil specimens with the aid of focused ion beam (FIB). Hence the interior crack progressing routes are illustrated and the atomic structure particularly at the most tip of cracks are characterized by using the high resolution TEM. It is revealed that the cracks mainly progress within a spinel phase (Cr2MnO4) while not its interface with neighbouring martensitic matrix. Moreover, geometric phase analysis (GPA) and lattice misfit at the most tip of cracks further manifest a elastic dominated and a plastic dominated mechanism corresponding to the two specimens, respectively. Cracking of the 650 °C specimen is mainly attributes to the accumulation of plastic strain that caused by the viscoelastic transformation of PAGBs, which causes intriguing periodic grain boundary sliding (GBS) waves ahead of the crack tip.