CuO nanowires with high crystalline quality are synthesized via a simple thermal oxidation method. Charge conduction on individual nanowires under a transverse electric field exhibits an intrinsic p-type semiconducting behavior. Variations in signal transducer in different chemical gas environments are measured on individual CuO nanowire field effect transistors. They demonstrate good performance to both NO(2) and ethanol gasses. In particular, the nanowire chemical sensor reveals a reverse response to ethanol vapor under temperature variation. Experimental results and first-principles calculations indicate that ethanol is oxidized in air at high temperature, resulting in the production of CO(2) and H(2)O. The strong H(2)O adsorption leads to the reversal behavior, due to the electron transfer from H(2)O molecules to the CuO surface.