Cu-CeO2/AC catalysts exhibited extraordinary catalytic performance in the upgradation of ethanol to n-butanol. To the best of our knowledge, this is the first report that the highest n-butanol yields of 21.6% and nearly 20% could be achieved over heterogeneous catalysts under mild reaction conditions in batch and fixed-bed reactors, respectively. The high catalytic activity, selectivity and stability of these catalysts could be ascribed to the synergy of Cu, CeO2 and the activated carbon support.