Understanding the roles of metals and atomic structures in activating various elementary steps of electro-catalytic reactions can help rational design of binary or ternary catalysts for promoting activity toward desirable products via favorable pathways. Here we report on a newly developed ternary Au@PtIr core-shell catalyst for ethanol oxidation reaction (EOR) in alkaline solutions, which exhibits an activity enhancement of 6 orders of magnitude compared to AuPtIr alloy catalysts. Analysis of in situ infrared reflection absorption spectra for Au@PtIr and its bimetallic subsets, Au@Pt and PtIr alloy, found that monatomic steps and Au-induced tensile strain on PtIr facilitate C-C bond splitting via ethanol dissociative adsorption and Ir promotes dehydrogenation at low potentials. As evidenced by the CO band being observed only for the PtIr alloy that is rather inactive for ethanol dissociative adsorption, we propose that splitting the C-C bond at the earliest stage of EOR activates a direct 12-electron full oxidation pathway because hydrogen-rich fragments can be fully oxidized without CO as a poisoning intermediate. The resulting synergy of complementary effects of Au core and surface Ir leads to an outstanding performance of Au PtIr for EOR as characterized by a low onset potential of 0.3 V and 8.3 A mg(all-metals)(-1) peak current with 57% currents generated via full ethanol oxidation.