A highly effective alcoholysis of ethylene-vinyl acetate (EVA) copolymers has been achieved to prepare ethylene-vinyl alcohol (EVOH) copolymers with various ethylene contents (30.2-49.5 mol %) having ca. 100% of alcoholysis degree even at a very low catalyst dosage. The kinetics show that the alcoholysis rate strongly depends on the composition and sequence of the EVA copolymer. The alcoholysis rate decreases with increasing E content and decreases in the order of VAcVAcVAc > VAcVAcE > EVAcE triad sequence. The formation of densely packed regions in EVOH from VVV, EVE, and EEE triad sequences along macromolecular chains via hydrogen bonds and crystallization makes a great contribution to inhibit oxygen transmission and thus to improve the barrier property. To the best of our knowledge, this is the first example to reveal the effect of sequence on alcoholysis of EVA and the oxygen barrier property of EVOH, which is profitable for macromolecular engineering of high performance EVOH copolymers.