In this study, in order to explore the failure mode of ZnO varistors under multiple lightning stroke, a 5-pulse 8/20 μs nominal lightning current with pulse intervals of 50 ms was applied to the 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 current were described. The performance changes of ZnO varistors after multiple lightning impulses were analyzed from macro and micro perspectives. According to the results of this study’s experiments, the macroscopic failure mode of the ZnO varistors after multiple lightning impulse was that the electrical parameters deteriorate rapidly with the increase of the number of impulse groups, and finally destroyed by side-corner cracking. The microstructural examination indicated that after the multiple lightning strokes, the proportion of Bi in the several crystal phases had been converted, the grain size of 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 current.