<p>H₂O activation plays a pivotal role in steering the activity and selectivity of electrochemical CO₂ reduction reaction (eCO₂RR). However, precisely tuning this process to favor eCO₂RR over the competing hydrogen evolution reaction (HER) remains a formidable challenge. Herein, we report a fluorine-doped La₂CuO₄ (F-LC) catalyst that significantly enhances CO₂ activation, H₂O dissociation and asymmetric C–C coupling by facilitating the hydrogenation of adsorbed CO (*CO) to form *CHO intermediate. The F-sites in F-LC accelerate interfacial H₂O dissociation via hydrogen bonding interactions, generating abundant active hydrogen (*H) species that facilitate the hydrogenation of *CO to *CHO. Moreover, the formation of a dense hydrogen-bond network on the F-LC surface reorganizes interfacial H₂O molecules, enhances proton transfer, and suppresses the competitive HER. These synergistic effects promote effective asymmetric *CO–*CHO coupling, leading to efficient multicarbon (C₂₊) products formation. As a result, F-LC achieves a Faradaic efficiency of up to 73.0% for C₂₊ products, significantly surpassing that of undoped LC (41.7%), thereby highlighting the crucial role of F doping in promoting interfacial H₂O activation and C–C coupling. This work offers a promising strategy to boost eCO₂RR to C₂₊ products by optimizing interfacial H₂O dissociation and enhancing CO₂ activation.</p>