AbstractAlthough Ru‐based materials are among the outstanding catalysts for the oxygen evolution reaction (OER), the instability issue still haunts them and impedes the widespread application. The instability of Ru‐based OER catalysts is generally ascribed to the formation of soluble species through the over‐oxidation of Ru and structural decomposition caused by involvement of lattice oxygen. Herein, an effective strategy of selectively activating the lattice oxygen around Ru site is proposed to improve the OER activity and stability. Our synthesized spinel‐type electrocatalyst of Ru and Zn co‐doped Co3O4 showed an ultralow overpotential of 172 mV at 10 mA cm−2 and a long‐term stability reaching to 100 hours at 10 mA cm−2 for alkaline OER. The experimental results and theoretical simulations demonstrated that the lattice oxygen site jointly connected with the octahedral Ru and tetrahedral Zn atoms became more active than other oxygen sites near Ru atom, which further lowered the reaction energy barriers and avoided generating excessive oxygen vacancies to enhance the structural stability of Ru sites. The findings hope to provide a new perspective to improve the catalytic activity of Ru‐incorporated OER catalysts and the stability of lattice‐oxygen‐mediated mechanism.