A new thiophene-2-carboxamide-functionalized Zr-UiO-66 MOF (1) was synthesized by employing a traditional solvothermal procedure. Compound 1 displayed high thermal (up to 340 °C under an Ar atmosphere) and chemical stability (in water, 1 M HCl, and acetic acid). A nitrogen physisorption measurement with the activated form of 1 (denoted 1') exhibited a BET surface area (781 m2/g) despite attachment of a bulky side chain with the linker molecule. Compound 1' was able to heterogeneously catalyze the ring-opening reaction of epoxides with amines. Catalyst 1' exhibited significant yields as well as wide substrate scope in the ring opening of epoxides by means of amines. It also displayed better catalytic performance in comparison to known MOF catalysts such as Cu3(BTC)2, Fe(BTC) (BTC: 1, 3, 5-benzenetricarboxylate), and Zr-UiO-66. Control experiments were performed with free linker, Zr(IV) salt and without catalyst 1', confirming the exclusive role of 1' in the catalytic reaction. The reusability characteristics of catalyst 1' was established for up to five consecutive catalytic cycles. The synthesis and characterization of the linker molecule, material 1, and 1' and mechanism of the catalysis reaction were studied elaborately.