Polycrystalline NiO thick film-based gas sensors have been exposed to different test gas atmospheres at 250 °C and measured via simultaneous electrical resistance and work function investigations. Accordingly, we decoupled different features manifested toward the potential changes, i.e., work function, band-bending, and electron affinity. The experimental results have shown that the presence of moisture induces an unusual behavior toward carbon monoxide (CO) detection by considering different surface adsorption sites. On this basis, we derived an appropriate detection mechanism capable of explaining the lack of moisture influence over the CO detection with NiO-sensitive materials. As such, CO might have both chemical and dipolar interactions with pre-adsorbed or lattice oxygen species, thus canceling out the effect of moisture. Additionally, morphology, structure, and surface chemistry were addressed, and the results have been linked to the sensing properties envisaging the role played by the porous quasispherical–hollow structures and surface hydration.