We directly measure the three-dimensional movement of intrinsic point defects driven by applied electric fields inside ZnO nano- and micro-wire metal–semiconductor–metal device structures. Using depth- and spatially resolved cathodoluminescence spectroscopy (CLS) in situ to map the spatial distributions of local defect densities with increasing applied bias, we drive the reversible conversion of metal–ZnO contacts from rectifying to Ohmic and back. These results demonstrate how defect movements systematically determine Ohmic and Schottky barriers to ZnO nano- and microwires and how they can account for the widely reported instability in nanowire transport. Exceeding a characteristic threshold voltage, in situ CLS reveals a current-induced thermal runaway that drives the radial diffusion of defects toward the nanowire free surface, causing VO defects to accumulate at the metal–semiconductor interfaces. In situ post- vs pre-breakdown CLS reveal micrometer-scale wire asperities, which X-ray photoelectron spectroscopy (XPS) finds to have highly oxygen-deficient surface layers that can be attributed to the migration of preexisting VO species. These findings show the importance of in-operando intrinsic point-defect migration during nanoscale electric field measurements in general. This work also demonstrates a novel method for ZnO nanowire refinement and processing.