The fatigue behavior of ZnO nanowires (NWs) and microwires was systematically investigated with in situ transmission electron microscopy electromechanical resonance method. The elastic modulus and mechanical quality factors of ZnO wires were obtained. No damage or failure was found in the intact ZnO wires after resonance for about 10(8)-10(9) cycles, while the damaged ZnO NW under electron beam (e-beam) irradiation fractured after resonance for seconds. The research results will provide a useful guide for designing, fabricating, and optimizing electromechanical nanodevices based on ZnO nanomaterials, as well as future applications.