99Tc is one of the most problematic radioisotopes in used nuclear fuel owing to its combined features of high fission yield, long half-life, and high environmental mobility. There are only a handful of functional materials that can remove TcO4- anion from aqueous solution and identifying for new, stable materials with high anion-exchange capacities, fast kinetics, and good selectivity remains a challenge. We report here an 8-fold interpenetrated three-dimensional cationic metal-organic framework material, SCU-100, which is assembled from a tetradentate neutral nitrogen-donor ligand and two-coordinate Ag+ cations as potential open metal sites. The structure also contains a series of 1D channels filled with unbound nitrate anions. SCU-100 maintains its crystallinity in aqueous solution over a wide pH range from 1 to 13 and exhibits excellent β and γ radiation-resistance. Initial anion exchange studies show that SCU-100 is able to both quantitatively and rapidly remove TcO4- from water within 30 min. The exchange capacity for the surrogate ReO4- reaches up to 541 mg/g and the distribution coefficient Kd is up to 1.9 × 105 mL/g, which are significantly higher than all previously tested inorganic anion sorbent materials. More importantly, SCU-100 can selectively capture TcO4- in the presence of large excess of competitive anions (NO3-, SO42-, CO32-, and PO43-) and remove as much as 87% of TcO4- from the Hanford low-level waste melter off-gas scrubber simulant stream within 2 h. The sorption mechanism is well elucidated by single crystal X-ray diffraction, showing that the sorbed ReO4- anion is able to selectively coordinate to the open Ag+ sites forming Ag-O-Re bonds and a series of hydrogen bonds. This further leads to a single-crystal-to-single-crystal transformation from an 8-fold interpenetrated framework with disordered nitrate anions to a 4-fold interpenetrated framework with fully ordered ReO4- anions. This work represents a practical case of TcO4- removal by a MOF material and demonstrates the promise of using this type of material as a scavenger for treating anionic radioactive contaminants during the nuclear waste partitioning and remediation processes.