Acetate is an essential raw material in the chemical industry, supporting sustainable processes and efficient carbon utilization, driving interest in electrochemical CO-to-acetate conversion. However, this process is limited by catalyst instability and the complexity of the reaction pathway, making precise control difficult. Herein, we engineer nanoconfined copper-organic interfaces within a series of nucleophilic substituted heterocyclic copper phthalocyanine covalent organic frameworks (CuPc-COFs) with AA’ stacking configuration to selectively steer CO electroreduction toward acetate. This architecture stabilizes low-coordination Cu clusters─generated via partial reduction of phthalocyanine Cu sites─and fosters synergistic CuPc-Cu cluster interactions, creating an active interfacial microenvironment that enhances acetate selectivity. The optimized CuPc-COF achieves a Faradaic efficiency (FE) of 53.5% for acetate at −0.9 V vs RHE. Operando X-ray absorption spectroscopy (XAS) confirms the in situ formation of highly reactive copper-organic interfaces, while in situ FTIR spectroscopy and DFT calculations reveal that low-coordinated Cu clusters strengthen *CO bridge adsorption (*CO_B) and promote *COCO dimerization. Additionally, heterocyclic linkers provide electron donation, stabilizing the Cu clusters and improving the structural integrity. This work elucidates the critical role of nanoconfined interface engineering in C-C coupling and establishes a design paradigm for advanced CO electroreduction catalysts.