By means of first-principles calculation, we explore the vacancy mechanism of titanium sesquioxide (Ti2O3) and further investigate the influence of vacancy on the electronic properties of Ti2O3. Two vacancy models are considered. We find that Ti2O3 prefers to form oxygen vacancy (O-va) in comparison to Ti vacancy (Ti-va) because the removed oxygen atom improves the localized hybridization between Ti and O. The low concentration of vacancies is more thermodynamic stability than that of high concentration of vacancies. In comparison to titanium dioxide (TiO2), Ti2O3 exhibits the metallic behavior due to the band overlap between the conduction band and the valence band. Importantly, we find that those vacancies enhance the electronic transport of Ti2O3 because the removed atom promotes the band overlaps at the Fermi level (EF). Display omitted •Vacancy mechanism of Titanium Sesquioxide is studied by first-principles calculations.•Ti2O3 exhibits the semiconductor-to-metal transition compared to the TiO2.•Ti2O3 prefers to form the O vacancy due to the strong localized hybridization between Ti and O.•Those vacancies enhance the electronic transport of Ti2O3.