Cu-based bimetallic catalysts have attracted great attention for the reverse water gas shift (RWGS) reaction due to their high activity and selectivity. This work reports the application of Cu-In bimetallic catalysts for the RWGS reaction and demonstrates that the promotion effect of In on Cu is support sensitive. The Cu-In/ZrO2 catalyst exhibited significantly higher CO2 conversion than the Cu/ZrO2 catalyst, whereas the CO2 conversion over Cu-In/CeO2 was much lower than that of Cu/CeO2. The reasons of the support-dependent RWGS activity was revealed by systematic characterizations. On the ZrO2 support, Cu and In formed Cu-In alloys and promoted the activation of CO2 by the oxygen vacancies from partially reduced In2O3. On the CeO2 support, Cu and In were in the form of metallic Cu and In2O3, respectively. The dispersion of Cu and the formation of oxygen vacancies on CeO2 were obstructed by the introduction of In, leading to decreased RWGS activity. Among these catalysts, Cu/CeO2 showed the best RWGS activity because of the strong CO2 activation ability of the partially reduced CeO2 support and the highly active Cu/CeO2-x interfaces. These results provide new insights into the design and understanding of supported bimetallic catalysts for CO2 hydrogenation.