Renewable　fatty　esters　are　a　class　of　clean　feedstock　to　produce　high　value-added　fatty　alcohols.　Herein,　the　hydrogenation　of　methyl　palmitate　(MP)　to　hexadecanol　over　defect-rich　Cu/m-ZrO2　catalysts　was　studied　systematically.　A　series　of　Cu/m-ZrO2　catalysts　with　different　concentrations　of　oxygen　vacancies　(Ovs)　were　fabricated　by　adjusting　the　calcination　temperature　of　m-ZrO2　support.　Among　the　catalysts,　Cu/m-ZrO2-350　displays　the　highest　Cu　dispersion,　the　largest　number　of　Cu0　sites　and　surface　Ov　concentration,　which　exhibits　the　best　activity　for　MP　hydrogenation.　It　gives　the　MP　conversion　of　94.6%　and　hexadecanol　yield　of　93.3%　at　300　°C　and　7.5　MPa　of　H2.　Spectroscopic　characterizations　and　theoretical　calculations　revealed　that　the　highly　dispersed　Cu　species　and　abundant　Ov　sites　synergistically　boost　the　hydrogenation　of　MP.　Specifically,　the　Cu0　sites　facilitate　the　heterolysis　of　H2,　and　the　Ov　sites　contribute　to　the　dissociation　of　MP.　The　synergistic　effect　of　Cu　species　and　Ov　sites　disclosed　in　this　work　provides　deep　insights　into　the　design　of　catalysts　for　efficient　conversion　of　fatty　esters　to　fatty　alcohols.　©　2023　American　Chemical　Society.