Electrochemical CO2 reduction to multi-carbon fuels and chemicals is intriguing but remains a challenge. Here, we report that a combination of Sn doping and creation of oxygen vacancies (V-O) can synergistically boost CO2 reduction to C2H4 over CuO nanosheets with an onset potential of 0.7 V (versus reversible hydrogen electrode). The activity and selectivity of CuO can be easily tuned by manipulation of Sn dopant and V-O contents. The Faradaic efficiency toward C2H4 formation over Sn-doped CuO(V-O) approaches 48.5% -h 1 2%, which maintains stability over 24 h at a mild overpotential, in contrast to a maximum of 26.8% +/- 2.2% over pristine CuO. The Sn-doped CuO(V-O) catalyst presents an approximately 2.3-fold improvement in C2H4 current compared to undoped CuO at similar overpotentials. Theoretical calculations further show that doping of VO-enriched CuO surface by Sn lowers the dimerization energy of adsorbed CO intermediate, thereby promoting C-C coupling to yield C2H4.