A self-assembly-formed triglycylglycine macrocyclic ligand (TGG(4-)) complex of Cu(II), RTGG(4-))Cu-II-OH2](2-), efficiently catalyzes water oxidation in a phosphate buffer at pH 11 at room temperature by a well-defined mechanism. In the mechanism, initial oxidation to Cu(III) is followed by further oxidation to a formal "Cu(IV)" with formation of a peroxide intermediate, which undergoes further oxidation to release oxygen and close the catalytic cycle. The catalyst exhibits high stability and activity toward water oxidation under these conditions with a high turnover frequency of 33 s(-1).