The catalytic oxidation of ethylbenzene (EB) into acetophenone (AP) is a vibrant area, with a growing number of researchers paying attention to this thematic investigation. Herein, we demonstrate that spinel-type (Co,Mn)(Co,Mn)2O4 can function as an efficient catalyst for the solvent-free oxidation of EB with molecular oxygen. The incorporation of Mn into the Co3O4 network can break the local structural symmetry of Co-O-Co linkages due to the bond competition, inducing the formation of an asymmetrical Co-O-Mn configuration with an electron local exchange interaction. The Co-O-Mn sites can facilitate the perturbation of nonpolar O2 and thus contribute to the generation of abundant •O2- species for initiating the oxidation of EB. We envision that this study not only provides a promising catalyst for EB oxidation but also affords a new insight into the design of advanced spinel oxides for selective oxidation reactions.