Metal–insulator transitions in strongly correlated transition metal oxides (TMOs) induced by electrochemical charging have been attributed to formation of vacancy defects. However, the role of native defects in affecting these transitions is not well understood. This presentation will discuss a new type of phase transition in p-type, nonstoichiometric nickel oxide involving a semiconductor-to-insulator-to-metal transition along with the complete reversal of conductivity from p- to n-type at room temperature induced by the interaction of native vacancy defects with redox species such as Li⁺ during electrochemical charging. Direct observation of vacancy-ion interactions using in-situ near-infrared photoluminescence spectroscopy show that this transition is a result of passivation of native nickel (cationic) vacancy defects and subsequent formation of oxygen (anionic) vacancy defects driven by Li⁺ insertion into the lattice. Changes in the oxidation states of nickel due to defect interactions probed by X-ray photoemission spectroscopy support the above conclusions. In contrast, n-type, nonstoichiometric tungsten oxide shows only insulator-to-metal transition, which is a result of oxygen vacancy formation. The defect-property correlations shown here in these model systems can be extended to other oxides to enable rational engineering of a new robust class of nanoscale, low temperature TMO catalysts and sensors having tailored functionality and selectivity.