The water-gas shift reaction (WGS, CO + H2O -> H-2 + CO2) was studied over CuO/CeO2 catalysts with two different ceria particle morphologies, in the form of nanospheres (ns) and nanocubes (nc). To understand the strong dependence of the WGS reaction activity on the ceria nanoshapes, pulses of CO (without and with water vapor) were employed during in situ X-ray diffraction and X-ray absorption near edge structure measurements done to characterize the catalysts. The results showed that CuO/CeO2 (ns) exhibited a substantially better activity than CuO/CeO2 (nc). The higher activity was associated with the unique properties of CuO/CeO2 (ns), such as the easier reduction of highly dispersed CuO to metallic Cu, the stability of metallic Cu and a larger concentration of Ce3+ in CeO2 (ns).