Density Functional Theory Calculations and Mechanistic Insights. To correlate the selectivity difference between Cu58 and Cu58-I NCs in electrochemical CO2RR with their structural/active-site difference, we carried out DFT calculations based on the computational hydrogen electrode (see SI for details). We excluded Cu₅₈-II nanoclusters from the study as HER is the main reaction pathway for this nanocluster. Our hypothesis is that at the negative enough overpotentials, both catalysts can effect CO2RR to CO but only Cu58-I NC can further reduce CO to CH3OH. To test this hypothesis, we computed the detailed CO2RR pathway from CO2 to CO and then to CH3OH on both Cu58 and Cu58-I NCs. As shown in Figure , we found that CO2 is weakly adsorbed on both clusters. Then we used the computational hydrogen electrode method and sequentially added H to CO2 and computed the intermediate adsorption energies. We found that formation of *COOH is more favourable than *HCOO (Figure ) and less uphill on Cu58-I than Cu58. Next step is CO formation from *COOH, which significantly favors Cu58-I than Cu58. After H2O desorption, *CO is converted to *CHO, which is the potential-limiting step in leading to CH3OH formation. On the Cu58 NC, CO desorption is easier than *CHO formation, while on the Cu58-I NC, *CHO is competitive against CO desorption. CO and CHO adsorb stronger on the Cu58-I NC than on the Cu58 NC. We think In summary, here in we reported a novel synthesis method for a surface ligand vacancyinduced Cu NCs, distinguished by their unique arrangement of metal atoms, deviating from the conventional regular configuration. The structural distortions significantly influence their catalytic behavior, particularly in electrochemical CO2RR. Through our electrochemical analyses, we have discovered an exceptional selectivity for CH₃OH production (FECH3OH is ~54% at -0.7 V vs. RHE), marking the defect-induced Cu58-I NC as the first to demonstrate direct electrochemical conversion of such product using NCs. In contrast, the regular Cu₅₈ NCs primarily produce CO, while the additional defects in the structural architecture promote HER pathways. DFT calculations of the CO2RR pathways attributed the selectivity toward CH3OH to enhanced binding of CO and CHO intermediates at the edge Cu site next to the vertex Cu site with a ligand vacancy; electronic structure analysis showed that the d-states of the edge Cu site shifted up due to the geometric distortion induced by the defect and the missing phosphine ligand, rendering the edge Cu site more active. Thus, this comprehensive approach not only elucidates the catalytic mechanism but also underscores the potential of tailored structural designs for enhancing electrochemical CO2 reduction efficiency. The following files are available free of charge. brief description (file type, i.e., PDF) brief description (file type, i.e., PDF)