Cation substitution in spinel cobaltites (e.g., ACo2O4, in which A = Mn, Fe, Co, Ni, Cu, or Zn) is a promising strategy to precisely modulate their electronic structure/properties and thus im-prove the corresponding electrochemical performance for water splitting. However, the fun-damental principles and mechanisms are not fully understood. This research aims to systemat-ically investigate the effects of cation substitution in spinel cobaltites derived from mixed-metal-organic frameworks on the oxygen evolution reaction (OER). Among the obtained ACo2O4 catalysts, FeCo2O4 showed excellent OER performance with a current density of 10 mAcm–2 at an overpotential of 164 mV in alkaline media. Both theoretical calculations and ex-perimental results demonstrate that the Fe substitution in the crystal lattice of ACo2O4 can sig-nificantly accelerate charge transfer, thereby achieving enhanced electrochemical properties. The crystal field of spinel ACo2O4, which determines the valence states of cations A, is identified as the key factor to dictate the OER performance of these spinel cobaltites.