Optimization of active sites and stability under irradiation are important targets for sorbent materials that might be used for iodine (I 2 ) storage. Herein, we report the direct observation of I 2 binding in a series of Cu(II)-based isostructural metal−organic frameworks, MFM-170, MFM-172, MFM-174, NJU-Bai20, and NJU-Bai21, incorporating various functional groups (−H, −CH 3 , − NH 2 , −C�C−, and −CONH−, respectively). MFM-170 shows a reversible uptake of 3.37 g g −1 and a high packing density of 4.41 g cm −3 for physiosorbed I 2 . The incorporation of −NH 2 and − C�C− moieties in MFM-174 and NJU-Bai20, respectively, enhances the binding of I 2 , affording uptakes of up to 3.91 g g −1 . In addition, an exceptional I 2 packing density of 4.83 g cm −3 is achieved in MFM-174, comparable to that of solid iodine (4.93 g cm −3 ). In situ crystallographic studies show the formation of a range of supramolecular and chemical interactions−C�C− sites, respectively, and adsorbed I 2 molecules. These observations have been confirmed via a combination of solid-state nuclear magnetic resonance, X-ray photoelectron, and Raman spectroscopies. Importantly, γ-irradiation confirmed the ultraresistance of MFM-170, MFM-174, and NJU-Bai20 suggesting their potential as efficient sorbents for cleanup of radioactive waste.