Water gas shift activity measurements for 12 transition metals (Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Re, Ir, Pt, Au) supported on inert MgAl2O4 and Ce0.75Zr0.25O2 are presented, to elucidate the influence of the active metal and the support. The activity is related to the adsorption energy of molecular CO and atomic oxygen on the metal; the latter is a good measure for the reactivity of the metal towards H2O. Generally, the activity of the catalysts with the Ce0.75Zr0.25O2 support is higher, compared to the corresponding MgAl2O4-supported catalysts. Exceptions are Cu and Au, which have a higher activity on the MgAl2O4 support and are both characterized by weak CO adsorption. For the MgAl2O4-supported catalysts a volcano-type relation between the activity and the adsorption energy of atomic oxygen on the metal is obtained. The maximum activity is found for metals with a binding energy of oxygen around −2.5 eV. No clear correlation exists with the adsorption energy of CO. In contrast, the activity for the Ce0.75Zr0.25O2 support increases with increasing adsorption strength for CO, and based on a relatively low activity of Cu the activity does not seem to depend on the adsorption energy of oxygen. Such a change in activity-descriptor for the different supports can be rationalized by the possibility that water dissociation occurs on the redox-active Ce0.75Zr0.25O2 support, whereas the MgAl2O4 support is inactive.