We report significant enhancement of CuO nanowire (NW) sensing performance at room temperature through the surface functionalization with SnO(2) nanocrystals (NCs). The sensitivity enhancement can be as high as ∼300% for detecting 1% NH(3) diluted in air. The improved sensitivity could be attributed to the electronic interaction between p-type CuO NWs and n-type SnO(2) NCs due to the formation of nanosized p-n junctions, which are highly sensitive to the surrounding gaseous environment and could effectively manipulate local charge carrier concentration. Our results suggest that the NC-NW structure is an attractive candidate for practical sensing applications, in view of its outstanding room-temperature sensitivity, excellent dynamic properties (rapid response and quick recovery), and flexibility in modulating the sensing performance (e.g., by adjusting the coverage of SnO(2) NCs on CuO NWs and doping of SnO(2) NCs).