Chemical looping provides an energy‐ and cost‐effective route for alkane utilization. However, there is considerable CO2 co‐production caused by kinetically mismatched O2− bulk diffusion and surface reaction in current chemical looping oxidative dehydrogenation systems, rendering a decreased olefin productivity. Sub‐monolayer or monolayer vanadia nanostructures are successfully constructed to suppress CO2 production in oxidative dehydrogenation of propane by evading the interference of O2− bulk diffusion (monolayer versus multi‐layers). The highly dispersed vanadia nanostructures on titanium dioxide support showed over 90 % propylene selectivity at 500 °C, exhibiting turnover frequency of 1.9×10−2 s−1, which is over 20 times greater than that of conventional crystalline V2O5. Combining in situ spectroscopic characterizations and DFT calculations, we reveal the loading–reaction barrier relationship through the vanadia/titanium interfacial interaction.