Development of highly active, durable, and low-cost electrocatalysts for energy conversion devices, such as electrolyzers and fuel cells, is a key to realizing “hydrogen economy” vision. The electrolyzers comprise two complementary redox reactions, oxygen evolution reaction (OER) at the anode and hydrogen evolution reaction at the cathode. In particular, the OER electrocatalyst is of pivotal importance, as this reaction involves an energetically manding four-electron transfer as well as the activation of oxygen molecule. We have endeavored to design high-performing OER electrocatalysts by controlling morphology and defect chemistry of the catalysts. We present precious metal-based, multimetallic, nanoframe catalysts, which allow for saving the usage of expensive precious metals and enhancing collision frequency of reactants. The catalyst composed of PtNi/RuO2 core/isosahedral nanoframe shell showed excellent activity and durability for the acidic OER. We show a series of perovskites with controlled defect site densities for the alkaline OER. A triple perovskite showed superior OER activity to single- and double- perovskites, which could be correlated with its oxygen defect–rich structure, lower charge transfer resistance, and smaller hybridization strength between O 2p and Co 3d orbitals.