Controlling the growth of semiconducting nanowires with desired properties on a reproducible basis is of particular importance in realizing the next-generation electronic and optoelectronic devices. Here, we investigate the growth of cupric oxide (CuO) nanowires by direct oxidation of copper-containing substrates at500∘Cfor 150 minutes at various oxygen partial pressures. The substrates considered include a low-purity copper gasket, a high-purity copper foil, compacted CuO andCu2Othin layers, and layered Cu/CuO and Cu/Cu2Osubstrates. The morphology, composition, and structure of the product CuO nanowires were analyzed using scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, selected area electron diffraction, X-ray diffraction, and UV-Visible absorption. Selected oxidation processes have been monitored using a thermogravimetric analyzer. The layering structure of the substrate after oxidation was analyzed to elucidate the growth mechanism of CuO nanowires.