Designing porous materials for C2H2 purification and safe storage is essential research for industrial utilization. We emphatically regulate the metal‐alkyne interaction of PdII and PtII on C2H2 sorption and C2H2/CO2 separation in two isostructural NbO metal–organic frameworks (MOFs), Pd/Cu‐PDA and Pt/Cu‐PDA. The experimental investigations and systematic theoretical calculations reveal that PdII in Pd/Cu‐PDA undergoes spontaneous chemical reaction with C2H2, leading to irreversible structural collapse and loss of C2H2/CO2 sorption and separation. Contrarily, PtII in Pt/Cu‐PDA shows strong di‐σ bond interaction with C2H2 to form specific π‐complexation, contributing to high C2H2 capture (28.7 cm3 g−1 at 0.01 bar and 153 cm3 g−1 at 1 bar). The reusable Pt/Cu‐PDA efficiently separates C2H2 from C2H2/CO2 mixtures with satisfying selectivity and C2H2 capacity (37 min g−1). This research provides valuable insight into designing high‐performance MOFs for gas sorption and separation.