In this study, in order to explore the failure mode of ZnO varistors under multiple lightning strokes, a five-pulse 8/20 μs nominal lightning current with pulse intervals of 50 ms was applied to ZnO varistors. Scanning electron microscopy (SEM) and X-ray diffractometry (XRD) were used to analyze the microstructure of the material. The failure processes of ZnO varistors caused by multiple lightning impulse currents were described. The performance changes of ZnO varistors after multiple lightning impulses were analyzed from both macro and micro perspectives. According to the results of this study’s experiments, the macroscopic failure mode of ZnO varistors after multiple lightning impulses involved the rapid deterioration of the electrical parameters with the increase of the number of impulse groups, until destruction occurred by side-corner cracking. The microstructural examination indicated that, after the multiple lightning strokes, the proportion of Bi in the crystal phases was altered, the grain size of the ZnO varistors became smaller, and the white intergranular phase (Bi-rich grain boundary layer) increased significantly. The failure mechanism was thermal damage and grain boundary structure damage caused by temperature gradient thermal stress, generated by multiple lightning currents.