Methanol synthesis via CO2 hydrogenation has attracted intensive research efforts, but is challenged with development of active and selective catalyst materials that would allow the reaction occurs under milder conditions and being economically more viable. Herein we report the use of bifunctional active sites and their synergy in promoting CO2 hydrogenation kinetics and selectivity. A series of Cu-In-Zr-O mixed oxide nanomaterials containing Cu and defective In2O3 active sites were synthesized and studied for the catalytic properties. Significantly higher CO2 conversion and methanol selectivity were achieved using the Cu-In-Zr-O compared to its non-copper counterpart In-Zr-O, revealing synergy between the two active sites. Insights into the mechanism and functionality of the two actives in CO2 hydrogenation catalysis were obtained with in situ DRIFTS study. A formate-methoxy-methanol pathway and the possible rate-limiting steps were discovered. The excellent selectivity property of the Cu-In-Zr-O was attributed to strong adsorption of CO2 to defective In2O3, which creates a large energy barrier that suppresses CO2 dissociation into CO. The promotion in CO(2)hydrogenation kinetics was attributed to cooperation between the bifunctional active sites, with Cu sites adsorb and provide active hydrogen atoms that hydrogenate adsorbed CO2 at adjacent defective In2O3 sites. The findings confirmed synergy between bifunctional sites in CO2 hydrogenation catalysis and provided a new concept in development of active and selective catalyst materials. (C) 2019 Elsevier Inc. All rights reserved.