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Surface states that induce depletion regions are commonly believed to control the transport of charged carriers through semiconductor nanowires. However, direct, localized optical, and electrical measurements of ZnO nanowires show that native point defects inside the nanowire bulk and created at metal-semiconductor interfaces are electrically active and play a dominant role electronically, altering the semiconductor doping, the carrier density along the wire length, and the injection of charge into the wire. We used depth-resolved cathodoluminescence spectroscopy to measure the densities of multiple point defects inside ZnO nanowires, substitutional Cu on Zn sites, zinc vacancy, and oxygen vacancy defects, showing that their densities varied strongly both radially and lengthwise for tapered wires. These defect profiles and their variation with wire diameter produce trap-assisted tunneling and acceptor trapping of free carriers, the balance of which determines the low contact resistivity (2.6 × 10 -3 Ω·cm -2 ) ohmic, Schottky (Φ ≥ 0.35 eV) or blocking nature of Pt contacts to a single nano/microwire. We show how these defects can now be manipulated by ion beam methods and nanowire design, opening new avenues to control nanowire charge injection and transport.