The efficient separation of acetylene (C₂H₂) from its mixture with carbon dioxide (CO₂) remains a challenging industrial process due to their close molecular sizes/shapes and similar physical properties. Herein, we report a microporous metal–organic framework (JNU-4) with square-planar mononuclear copper(II) centers as nodes and tetrahedral organic linkers as spacers, allowing for two accessible binding sites per metal center for C₂H₂ molecules. Consequently, JNU-4 exhibits excellent C₂H₂ adsorption capacity, particularly at 298 K and 0.5 bar (200 cm³ g⁻¹). Detailed computational studies confirm that C₂H₂ molecules are indeed predominantly located in close proximity to the square-planar copper centers on both sides. Breakthrough experiments demonstrate that JNU-4 is capable of efficiently separating C₂H₂ from a 50 : 50 C₂H₂/CO₂ mixture over a broad range of flow rates, affording by far the largest C₂H₂ capture capacity (160 cm³ g⁻¹) and fuel-grade C₂H₂ production (105 cm³ g⁻¹, ≥98% purity) upon desorption. Simply by maximizing accessible open metal sites on mononuclear metal centers, this work presents a promising strategy to improve the C₂H₂ adsorption capacity and address the challenging C₂H₂/CO₂ separation.