Efficient electrochemical transformations of molecular oxygen (oxygen reduction and evolution) for energy conversion/storage rely largely on the effective design of heterogeneous electrocatalysts. Tuning the electrocatalytic properties of materials by controlling the electronic structure of active sites is a promising but challenging approach. Structural and compositional flexibilities of nonstochiometric mixed metal oxides present unique opportunities toward this goal, as the reactivity of their metal cationic centers can be modified via ligand and charge transfer modes. Herein, theoretical calculations combined with experiments demonstrate that highly catalytically active 4d/5d transition metal cations for oxygen reduction can be generated by tuning the distinct intrinsic oxophilicity of 3d and 4d/5d metal cations within a perovskite structure. Tailoring the perovskite composition is shown to switch catalytically poor Rh in supported catalysts to highly catalytic active Rh cationic centers within a perovskite framework (LaNi1–x Rh x O3, x ≤ 0.01). These findings open up opportunities for extrapolating the function of such catalytic systems to other targeted chemistries.