Cyclohexane oxidation into a ketone−alcohol mixture (KA oil) or adipic acid is an industrially significant reaction. Transition metal (TM) ion, as a core component of supported metal oxide catalysts, plays a significant role in cyclohexane oxidation. The mechanism of interaction between the transition metal ion and C−H bond in cyclohexane remains unexplored in the literature. In this study, various transition metal (Cr, Mn, Fe, Co, Ni, Cu, and Zn) ion-substituted CeO 2 catalysts have been prepared, characterized, and tested for catalytic activities in cyclohexane oxidation using O 2 as the oxidant. The average rate of cyclohexane conversion over the unit surface of the catalysts has been calculated to evaluate the intrinsic catalytic reactivity of the TM ions substituted in the CeO 2 lattice. The average rate, normalized with respect to the number of Cr ions over the unit surface (in 10% Cr/CeO 2 ), was the parameter to find the most active TM ion for the reaction. The mechanistic pathway of C−H activation over the TM ions-substituted CeO 2 catalysts has been supported by DFT calculations, indicating the formation of a reactive cyclohexene intermediate for the first time. Therefore, the rates of conversion of cyclohexane and cyclohexene over the Cu/CeO 2 catalyst have been calculated to determine the relative reactivity of the intermediate. The reactivity of the metal ions, in terms of the average rate of conversion, has been correlated to the electronic state of the doped transition metal ions.