Hydrogen sensing is becoming one of the hottest topics in the chemical sensing field, due to its wide number of applications and the dangerousness of hydrogen leakages. For this reason, research activities are focusing on the development of high-performance materials that can be easily integrated in sensing devices. In this work, we investigated the influence of Nb on the sensing performances of WO3 nanowires (NWs) synthetized by a low-cost thermal oxidation method. The morphology and the structure of these Nb-WO3 nanowires were investigated by field emission scanning electron microscope (FE-SEM), high-resolution transmission electron microscope (HR-TEM), X-ray diffraction (XRD), Raman and X-ray photoelectron (XPS) spectroscopies, confirming that the addition of Nb does not modify significantly the monoclinic crystal structure of WO3. Moreover, we integrated these NWs into chemical sensors, and we assessed their performances toward hydrogen and some common interfering compounds. Although the hydrogen sensing performances of WO3 nanowires were already excellent, thanks to the presence of Nb they have been further enhanced, reaching the outstanding value of more than 80,000 towards 500 ppm @ 200 °C. This opens the possibility of their integration in commercial equipment, like electronic noses and portable devices.