<p>Breaking the structural symmetry of active sites in single-atom catalysts (SACs) allows efficient regulation of the electron distribution around the metal centers, holding great promise for promoting their performance in electrocatalytic carbon dioxide reduction reaction (ECO₂RR). Herein, we propose a vacancy-engineering strategy for constructing asymmetric carbon-nickel-chlorine (C–Ni–Cl) sites in Ni SAC (Ni₁-C/Cl). In strongly acidic media (pH=1), Ni₁-C/Cl achieves Faradaic efficiency over 98% for carbon monoxide (CO) product at the operated current density of 500 mA cm⁻². In situ X-ray absorption spectra reveal that during electrocatalysis, the C₃–Ni–Cl sites exhibit potential-dependent structure evolutions, which can optimize their adsorption configurations for the reactive species. Theoretical calculations demonstrate that the Ni–C/Ni–Cl co-coordination induces the asymmetric electron distribution in C₃–Ni–Cl sites, resulting in the regulation of the electronic properties of the Ni centers, thereby optimizing the reaction pathway of CO₂-to-CO on these single-atom sites. This work extends the synthesis of SACs containing asymmetric single-atom sites, provides insights into designing industrial-oriented electrocatalysts toward other important electrocatalytic reactions.</p>