Cu2O surface with the coordinatively unsaturated Cu sites reveals advantages in the electroreduction of CO2 toward C2H4 production. Understanding the role of *CO coverage and veritable active sites is of great significance for a good command of the catalytic mechanism. Herein, based on density functional theory, the effects of *CO coverage during the reduction of CO2 to C2H4 on various active sites of Cu2O(111) surface, in terms of the adsorption and structural changes of *CO and key intermediates; the energy profiles of the C–C coupling steps; and the subsequent reaction mechanisms were investigated. Results show that CuCUS on the Cu2O(111) surface is especially reactive toward the *CO adsorption and subsequent reactions, being the preferred site owing to the unsaturated Cu atoms. The *CO coverage obviously tunes the adsorption stability of *COH and *CHO intermediates by affecting the adsorbent–adsorbent interactions. Higher coverage of *CO within 0.13–0.25 promotes the C–C coupling by lowering the energy barrier of *CH2 dimerization, favoring the C2H4 production. Due to the more facile generation of *CHO than *COH, the rate-determining step is speculated to be the C–C coupling with the highest barrier energy occurring in the *CHO pathway. Results provide a fundamental understanding of the CO2 reduction mechanism on Cu-based surfaces, favoring novel catalysts, rational design, and chemical fuel production.