Tailoring microstructures represents a daunting goal in materials science. Here, an innovative proposition is to utilize grain boundary (GB) complexions (a.k.a. interfacial phases) to manipulate microstructural evolution, which is challenging to control via only temperature and doping. Herein, we use ZnO as a model system to tailor microstructures using applied electric fields as a new “knob” to control GB structures locally via field-driven defects polarization. Specifically, continuously graded microstructures are created under applied electric fields. By employing aberration-corrected scanning transmission electron microscopy (AC STEM) in conjunction with density functional theory (DFT) and ab initio molecular dynamics (AIMD), we discover cation-deficient, oxygen-rich GBs near the anode with enhanced GB diffusivities. In addition, the field-driven redistribution of cation vacancies is deduced from a defect chemistry model, and subsequently verified by spatially resolved photoluminescence spectroscopy. This bulk defects polarization leads to preferential formation of cation-deficient (oxidized) GBs near the anode to gradually promote grain growth towards the anode. This mechanism can be utilized to create continuously graded microstructures without abnormal grain growth typically observed in prior studies. This study exemplifies a case of tailoring microstructural evolution via altering GB complexions locally with applied electric fields, and it enriches fundamental GB science.