The　high　activity　of　ethyl　acetate　(EA)　combustion　is　studied　over　the　CuO/CeO2　catalysts　which　are　prepared　by　the　ball　milling　method,　and　the　relationships　between　catalytic　activity　and　active　sites　of　CuO　and　Cu–O–Ce　structure　are　investigated.　The　finely　dispersed　CuO　particles　(around　1.0 nm)　and　Cu–O–Ce　structure　are　prepared　in　the　CuO/CeO2　catalysts　when　5 wt%　Cu　loading　is　acquired　with　the　calcination　temperature　at　500 °C.　Complete　conversion　of　ethyl　acetate　to　CO2　is　achieved　at　210 °C.　Via　controlling　calcination　temperatures　and　treatments　by　alkaline/acid,　it　is　demonstrated　that　the　synergistic　effect　between　highly　dispersed　CuO　and　Cu–O–Ce　structure　results　in　a　better　ability　of　oxygen　activation　and　catalytic　activity　for　the　5-CuO/CeO2(500)　catalyst.　This　study　provides　a　feasible　strategy　for　designing　an　efficient　CuO/CeO2　catalyst　and　an　insight　into　the　structure–activity　relationship.　©　The　Author(s),　under　exclusive　licence　to　Springer　Nature　B.V.　2024.