To achieve substantial reductions in CO2 emissions, catalysts for the photoreduction of CO2 into value-added chemicals and fuels will most likely be at the heart of key renewable-energy technologies. Despite tremendous efforts, developing highly active and selective CO2 reduction photocatalysts remains a great challenge. Herein, a metal oxide heterostructure engineering strategy that enables the gas-phase, photocatalytic, heterogeneous hydrogenation of CO2 to CO with high performance metrics (i.e., the conversion rate of CO2 to CO reached as high as 1400 µmol g cat−1 h−1) is reported. The catalyst is comprised of indium oxide nanocrystals, In2O3−x(OH)y, nucleated and grown on the surface of niobium pentoxide (Nb2O5) nanorods. The heterostructure between In2O3−x(OH)y nanocrystals and the Nb2O5 nanorod support increases the concentration of oxygen vacancies and prolongs excited state (electron and hole) lifetimes. Together, these effects result in a dramatically improved photocatalytic performance compared to the isolated In2O3−x(OH)y material. The defect optimized heterostructure exhibits a 44-fold higher conversion rate than pristine In2O3−x(OH)y. It also exhibits selective conversion of CO2 to CO as well as long-term operational stability.