© 2019 Elsevier B.V. This paper deals with CuO/ZrO2 catalysts with extremely high Cu loading and their catalytic activity for CO2 hydrogenation to methanol. Because of aiming an industrial application, we chose a flame spray pyrolysis (FSP) technique as a simple and rapid catalyst preparation method. Thanks to the FSP, we succeeded to prepare 20–80 wt% CuO/ZrO2 catalysts. Interestingly, the catalyst structure changed with the Cu loading. In the case of Cu loading = 20 wt%, CuO nanoparticles (ca. 5 nm) were supported on tetragonal ZrO2 particles (5–10 nm), observed by high-angle annular dark-field scanning transmission electron microscopy. Of note, the catalyst with 60 wt% of Cu was ZrO2@CuO core-shell nanoparticles: ZrO2 aggregates were covered with many CuO nanoparticles (<5 nm). When the Cu loading was 80 wt%, crystalline CuO particles (ca. 10 nm) as well as CuO nanoparticles (<5 nm) were supported on the above ZrO2 aggregates. The catalysts reduced by H2 at 300 °C consisted of Cu nanoparticles (<20 nm) and ZrO2 nanoparticles (5–10 nm). With decreasing the Cu loading, the interaction between the Cu and the ZrO2 became strong. The strong interaction caused high selectivity to methanol. In contrast to 20 wtCu% CuO/ZrO2, 80 wtCu% CuO/ZrO2 contained a large number of active sites for CO2 conversion, while the interaction between Cu and ZrO2 was weak. Therefore, the catalyst exhibited high yield and low selectivity to methanol. Among the prepared catalysts, at Cu loading = 60 wt%, the catalytic performance was better than that of a commercial CuO/ZnO/Al2O3. This is because the catalyst combined the advantages of both the 20 wt% CuO/ZrO2 (Cu-ZrO2 interaction) and the 80 wt% CuO/ZrO2 (a large number of active sites).