This paper presents a low cycle fatigue (LCF) failure analysis on [001], [011], and [111] orientations of a Ni‐based single crystal superalloys at 850 °C. Fracture mechanism and microstructure damage evolution are revealed through crystal plastic theory and fracture morphology analysis. Strain‐controlled LCF tests are conducted with the standard round bar samples; the fracture morphology and microstructure characteristics, such as the fracture mechanism and microstructure damage evolution, are observed via scanning electron microscopy (SEM), optical microscopy (OM). Crystal plastic theory is adopted to establish the crystal slip system framework, considering elastic and plastic strain rate, elastic orientation factors, and the resolved shear stress (Rss). The life prediction model is established based on Levkovitch damage theory, theoretical analysis, and test results has good consistency. The results demonstrate that fatigue life on [001] orientation is the longest, but considering the effects of stress amplitude and Young's modulus, [011] orientation exhibits the best fatigue performance. Under LCF loading, the initial crack starts to occur on surface of specimen if the internal defects are small and negligible; in contrast the initial crack starts to occur in subsurface or internal of specimen if the microstructure defects exist in material. The LCF cross‐section of SC belongs to the quasi‐cleavable type, the crack propagates in the direction of {111} plane and then extends along the vertical stress axis until the specimen fractures.