Large-scale CuO nanowires were in situ grown on Cu substrate by a very simple catalyst-free thermal oxidation process in atmosphere. The structure characterization revealed that these nanowires are monoclinic structured single crystallites with mean diameters of 60–200 nm. The effects of growth time and temperature on the morphology of the nanowires were investigated. It is found that the growth time has an important effect on the length and density of the nanowires, whereas the growth temperature has a distinct influence on the nanowire diameter. Different from the vapor–solid (V–S) mechanism, the growth of nanowires is found to be based on the Cu ion diffusion. The ethanol-sensing properties of these CuO nanowires were also studied based on a self-designed prototype and the results indicated that these large-scale nanowires are indeed a good candidate for gas-sensing applications.