Semiconducting oxides with reducible cations are ideal platforms for various functional applications in nanoelectronics and catalysts. Here we report an ultrathin monolayer α-MoO3 in which tunable electronic properties and different gas adsorbing behaviors are achieved upon the introduction of oxygen vacancies (VO). A unique property of α-MoO3 is that it contains three different types of oxygen atoms occupying three Wyckoff sites that are absent in other low-dimensional oxides and provides rich electronic hybridized states. The presence of VO triggers an intermediate state in the gap at ∼0.59 eV below the conduction band minimum and reduces the work function dramatically, together with new excitations at the near infrared. The realigned Fermi level associated with the dangling state of VO reduces the neighboring Mo atoms and affects gas adsorption thereafter. The binding energy of H2O molecules above VO is 2.5 times, up to-0.75 eV compared with that of a perfect lattice site and trends for the transfer of electrons are also reversed. The latter is related to the shallow localized state in the band gap due to H2O adsorbed above perfect MoO3 which becomes quenched upon adsorbing at the VO site. The rich in-gap defective states in oxygen deficient MoO3, broadening the light absorption and promoting the uptake of water, are conducive to the application of α-MoO3 for optoelectronics, photothermal therapy, and sensing of moisture.