Nafion ionomer, composed of hydrophobic perfluorocarbon backbones and hydrophilic sulfonic acid side chains, is the most widely used additive for preparing catalyst layers (CLs) for electrochemical CO₂ reduction, but its impact on the performance of CO₂ electrolysis remains poorly understood. Here, we systematically investigate the role of the catalyst ink formulation on CO₂ electrolysis using commercial CuO nanoparticles as the model pre-catalyst. We find that the presence of Nafion is essential for achieving stable product distributions due to its ability to stabilize the catalyst morphology under reaction conditions. Moreover, the Nafion content and solvent composition (water/alcohol fraction) regulate the internal structure of Nafion coatings, as well as the catalyst morphology, thereby significantly impacting CO₂ electrolysis performance, resulting in variations of C₂₊ product Faradaic efficiency (FE) by >3×, with C₂₊ FE ranging from 17 to 54% on carbon paper substrates. Using a combination of ellipsometry and in situ Raman spectroscopy during CO₂ reduction, we find that such selectivity differences stem from changes to the local reaction microenvironment. In particular, the combination of high water/alcohol ratios and low Nafion fractions in the catalyst ink results in stable and favorable microenvironments, increasing the local CO₂/H₂O concentration ratio and promoting high CO surface coverage to facilitate C₂₊ production in long-term CO₂ electrolysis. Therefore, this work provides insights into the critical role of Nafion binders and underlines the importance of optimizing Nafion/solvent formulations as a means of enhancing the performance of electrochemical CO₂ reduction systems.