We have devised a sensor system comprising p-CuO/n-ZnO core-shell nanofibers (CS nanofibers) for the detection of reducing gases with a very low concentration. The CS nanofibers were prepared by a two-step process as follows: (1) synthesis of core CuO nanofibers by electrospinning, and (2) subsequent deposition of uniform ZnO shell layers by atomic layer deposition. We have estimated the sensing capabilities of CS nanofibers with respect to CO gas, revealing that the thickness of the shell layer needs to be optimized to obtain the best sensing properties. It is found that the p-CuO/n-ZnO CS structures are suitable for detecting reducing gases at extremely low concentrations. The associated sensing mechanism is proposed on the basis of the radial modulation of an electron-depleted region in the shell layer.