The catalytic performance of vanadia supported on silica, alumina, zirconia, and titania was investigated in the selective oxidation of ethanol. It was shown that the activity and product distribution strongly depend on the support material, which determines the structure of supported vanadia species. On silica and alumina, low-active V2O5 crystallites were mainly formed regardless of the vanadium content. These catalysts demonstrated high selectivity toward only acetaldehyde. In contrast, monomeric surface vanadia species and polymeric surface vanadia species were mainly formed over TiO2 when the vanadium content did not exceed what is necessary for the ideal monolayer. Over zirconia, both the surface vanadia species and the V2O5 crystallites existed regardless of the vanadium content. It was found that the surface vanadia species are more active in the selective oxidation of ethanol than the V2O5 crystallites. The highest activity was observed for the polymeric vanadia species and, correspondingly, the best catalytic performance was achieved on the monolayer V2O5/TiO2 catalyst. At low temperatures between 110 and 150 °C, this catalyst demonstrated high activity in the oxidation of ethanol to acetaldehyde with the selectivity ranging between 80% and 100%. At temperature near 200 °C, the same catalyst was active in the oxidation of ethanol to acetic acid with the selectivity of approximately 65%. The surface intermediates and the catalyst state were also studied in situ by X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. It was shown that under reaction conditions near 100 °C, non-dissociatively adsorbed molecules of ethanol, ethoxide species, and adsorbed acetaldehyde exist on the catalyst surface, while at higher temperatures, V2O5/TiO2 is mainly covered with acetate species. Titanium cations remained in the Ti4+ state, whereas V5+ cations underwent a reversible reduction under reaction conditions. On the basis of the in situ data complemented by the results of kinetic measurements, a reaction mechanism for the selective oxidation of ethanol to acetaldehyde and acetic acid over the monolayer catalysts was proposed.