The high porosity, excellent water stability and optimized supramolecular host–guest interactions of MOFs are the three key factors for their potential practical applications in many important areas including gas storage/separation, catalysis and so on. In this study, we designed and constructed a highly porous (3, 36)-connected txt-type acylamide-functionalized metal–organic framework (HNUST-8) from a pyridine-based acylamide-linking diisophthalate and dicopper(II)-paddlewheel clusters. Interestingly, HNUST-8 possesses an exceptionally water-stable framework with a high BET surface area of about 2800 m² g⁻¹. At 298 K, HNUST-8 exhibits a high excess CO₂ uptake of 19.7 mmol g⁻¹ at 40 bar, an excellent total CH₄ storage capacity of 223 cm³(STP) cm⁻³ with a large working capacity of 178 cm³(STP) cm⁻³ at 80 bar, as well as highly efficient CO₂/CH₄ and CO₂/N₂ separation under dynamic conditions at 1 bar. Moreover, with the Lewis acidic open copper(II) sites and Lewis basic acylamide groups integrated into the framework, HNUST-8 demonstrates efficient catalytic activity as an acid–base cooperative catalyst in a tandem one-pot deacetalization–Knoevenagel condensation reaction.