The catalytic oxidation of ethyl acetate (EA) was studied over CuO/CeO₂ catalysts which were prepared by ball milling with different precursors (copper oxide, cerium acetate, cerium dioxide, copper acetate and cerium hydroxide). The CuO/CeO₂ catalyst (O-A) prepared with copper oxide and cerium acetate as precursors shows very high catalytic activity that 100% EA conversion is achieved at low temperature of 220 °C. It is found that specific surface area (112.8 m²/g), particle size of CuO (3.5 nm) and proportion of oxygen vacancies are prominent on the O-A catalyst. Oxygen vacancies in CeO₂ support are beneficial to enhancing the adsorption and activation of the oxygen. More finely dispersed CuO particles and oxygen vacancies which are derived from the synergistic interaction of Cu–Ce species play an important role in the catalytic oxidation of EA.