This paper presents a ZnO-CuO p-n hetero-junction chemiresistive sensor that comprises CuO hollow nanocubes attached to ZnO spherical cores as active materials. These ZnO-CuO core-hollow cube nanostructures exhibit a remarkable response of 11.14 at 1 ppm acetone and 200 degrees C, which is a superior result to those reported by other metal-oxide-based sensors. The response can be measured up to 40 ppb, and the limit of detection is estimated as 9 ppb. ZnO-CuO core-hollow cube nanostructures also present high selectivity toward acetone against other volatile organic compounds and demonstrate excellent stability for up to 40 days. The outstanding gas-sensing performance of the developed nanocubes is attributed to their uniform and unique morphology. Their core-shell-like structures allow the main charge transfer pathways to pass the interparticle p-p junctions, and the p-n junctions in each particle increase the sensitivity of the reactions to gas molecules. The small grain size and high surface area of each domain also enhance the surface gas adsorption.