The　chloride-mediated　ethylene　oxidation　reaction　(EOR)　of　ethylene　chlorohydrin　(ECH)　via　electrocatalysis　is　practically　attractive　because　of　its　sustainability　and　mild　reaction　conditions.　However,　the　chlorine　oxidation　reaction　(COR),　which　is　essential　for　the　above　process,　is　commonly　catalyzed　by　dimensionally　stable　anodes　(DSAs)　with　high　contents　of　precious　Ru　and/or　Ir.　The　development　of　highly　efficient　COR　electrocatalysts　composed　of　nonprecious　metals　or　decreased　amounts　of　precious　metals　is　highly　desirable.　Herein,　we　report　a　modified　Co3O4　with　a　single-atom　Ir　substitution　(Ir1/Co3O4)　as　a　highly　efficient　COR　electrocatalyst　for　chloride-mediated　EOR　to　ECH　in　neutral　seawater.　Ir1/Co3O4　achieves　a　Faradaic　efficiency　(FE)　of　up　to　94.8　%　for　ECH　generation　and　remarkable　stability.　Combining　experimental　results　and　density　functional　theory　(DFT)　calculations,　the　unique　atomically　asymmetrical　Ir−O−Co　configuration　with　a　strong　electron　coupling　effect　in　Ir1/Co3O4　can　accelerate　electron　transfer　to　increase　the　reaction　kinetics　and　maintain　the　structural　stability　of　Co3O4　during　COR.　Moreover,　a　coupling　reaction　system　integrating　the　anodic　chloride-mediated　and　cathodic　H2O2-mediated　EOR　show　a　total　FE　of　~170　%　for　paired　electrosynthesis　of　ECH　and　ethylene　glycol　(EG)　using　ethylene　as　the　raw　material.　The　technoeconomic　analysis　highlights　the　promising　application　prospects　of　this　system.　©　2024　Wiley-VCH　GmbH.