CO　hydrogenation　to　isobutyl　alcohol　is　a　promising　route　for　CO　transformation　to　high　value-added　products.　However,　the　formation　mechanism　of　isobutyl　alcohol　is　complex,　and　its　synthesis　requires　complex　catalysts　and　harsh　reaction　conditions,　which　hinders　the　identification　of　active　sites.　Herein,　we　efficiently　synthesized　isobutyl　alcohol　under　mild　conditions　over　a　simple　Cu-ZrO2　catalyst　by　decreasing　the　Cu　loading.　The　space-time　yield　(STY)　of　isobutyl　alcohol　using　an　optimal　CZ-0.11　catalyst　was　as　high　as　61.3　g·Lcat-1·h-1　with　a　CO　conversion　of　19.2%,　far　surpassing　the　STY　of　the　state-of-the-art　isobutyl　alcohol　synthesis　(44.6　g·Lcat-1·h-1)　under　harsh　conditions.　Decreasing　the　Cu　loading　increased　the　distribution　of　smaller　Cu　particles　and　clarified　the　structure-activity　relationship　of　Cu-Zr　interactions　for　isobutyl　alcohol　synthesis.　The　enhanced　Cu-Zr　interaction　led　to　the　formation　of　more　electron-deficient　Cu　species　on　the　CZ-0.11　catalyst,　which　enriched　the　linearly　adsorbed　CO　on　Cu,　as　demonstrated　by　in　situ　diffuse　reflectance　infrared　Fourier-transform　spectroscopy.　Experimental　and　theoretical　results　revealed　that　coupling　of　the　bicarbonate　species　on　ZrO2　with　the　linearly　adsorbed　CO　species　on　electron-deficient　Cu　clusters　promoted　the　formation　of　C2　intermediates　and　finally　produced　isobutyl　alcohol　through　rapid　β-addition.　These　insights　into　the　active　sites　for　CO　hydrogenation　to　isobutyl　alcohol　may　guide　further　catalyst　designs.　©　2023　American　Chemical　Society.