Uranium is the main source for nuclear energy but also one of the most toxic heavy metals. The current methods for uranium removal from water present limitations, such as narrow pH operating range, limited tolerance to high salt concentrations, or/and high cost. We show here that a layered sulfide ion exchanger K2MnSn2S6 (KMS-1) overcomes these limitations and is exceptionally capable in selectively and rapidly sequestering high (ppm) as well as trace (ppb) quantities of UO22+ under a variety of conditions, including seawater. KMS-1 can efficiently absorb the naturally occurring U traces in seawater samples. The results presented here reveal the exceptional potential of sulfide-based ion-exchangers for remediating of uranium-containing wastes and ground-water and for extracting uranium from the sea.