Here, we used NO as a test gas to propose a strategy for a nanowire gas sensor with the maximum response—the lowest detection limits. The apparatus uses an open space ensemble structure of nanowires with diameters at near total-depletion. For this purpose, a series of open space nanowire structures of WO3 was fabricated with diameters varying from 35 to 82 nm, and a corresponding conduction nanowire sensor model was proposed. The nanowire structures revealed the highest response and a lowest detection limit of 30 ppb. Furthermore, the sensor response was maximum with nanowires of ∼40 nm, which is the diameter corresponding to total depletion conditions; the response was decreased at smaller diameters. The sensor model successfully explained the ultimate lower limits of the size effect in the nanowire sensors. To realize optimum sensor performance with the practical ensemble type nano-structures, an open space morphology is critical to remove the effect of gas diffusion throughout the structure.