Catalytic carbon dioxide (CO2) hydrogenation to carbon monoxide (CO) via reverse water-gas shift (RWGS) reaction is of particular interest due to its direct use in various industrial processes as feedstock. However, the competitive CO2 methanation process severely limits the RWGS reaction in a lower temperature range. In this context, we propose a novel nanocatalyst (NC) comprising oxygen vacancy-enriched subnanometer-scale CoPd hybrid cluster (CoOxVPd)-anchored Pd nanoparticles (NPs) on cobalt oxide support underneath (denoted as CP-CoOxVPd) by using a galvanic replacement reaction-assisted wet chemical reduction method. As-developed CP-CoOxVPd NC initiated the RWGS reaction at 423 K temperature while showing an optimum CO production yield of ∼3414 μmol g−1catalyst and a CO selectivity as high as ∼99% at 523 K in the reaction gas of CO2:H2 = 1:3. The results of physical characterizations along with electrochemical and gas chromatography (GC) suggest that abundant oxygen vacancies in the surface-anchored CoOxVPd clusters are vital for CO2 adsorption and subsequent activation, while neighboring Pd domains facilitate the H2 dissociation. The obtained results are expected to provide a feasible design of Co-based NCs for the RWGS reaction.