Interphases are critical in electrochemical systems, influencing performance by controlling ion transport and stability. This study explores a metal-organic interphase in the electrocatalytic reduction of CO₂ (CO₂RR) on Cu, extending the concept of interphases to CO₂ conversion. Investigating organic modifications on CuO_x, we discover metal-organic interphases over 10 nm thick in highly ethanol-selective systems, contrary to the expected monolayer adsorption. Using an automated platform, 1080 CO₂RR experiments with 180 molecular modifiers identify functional groups affecting selectivity for ethanol and multi-carbon (C₂₊) products. We find that these modifiers consistently produce metal-organic interphases on the Cu or CuO_x surface. These interphases modulate Cu coordination, CO₂RR intermediates, and interfacial water configuration, significantly improving electrocatalytic performance. Testing across 11 CuO_x-based catalysts validates this approach, culminating in the development of two electrocatalysts that achieve ~80% faradaic efficiency for C₂₊ products with ethanol partial current densities up to 328 and 507 mA cm⁻². This study highlights the pivotal role of interphases in CO₂RR, advancing CO₂ conversion technologies.