Microscopic and spectroscopic analyses of uranium-contaminated sediments from select locations at the U.S. Department of Energy (DOE) Hanford site have revealed that sorbed uranium (U) often exists as uranyl precipitates associated with intragrain fractures of granitic clasts. The release of U to contacting fluids appears to be controlled by intragrain ion diffusion coupled with the dissolution kinetics of the precipitates that exist in the form of Na-boltwoodite. Here we present a coupled microscopic reactive diffusion model for the contaminated sediment on the basis of experimental measurements of intragrain diffusivity in the granitic lithic fragments and the dissolution kinetics of synthetic Na-boltwoodite. Nuclear magnetic resonance, pulse gradient spin echo measurements showed that the intragrain fractures of the granitic clasts isolated from the sediment contained two domains with distinct diffusivities. The fast diffusion domain had an apparent tortuosity of 1.5, while that of the slow region was two orders of magnitude larger. A two-domain diffusion model was assembled and used to infer the geochemical conditions that led to intragrain uranyl precipitation during waste-sediment interaction. Rapid precipitation of Na-boltwoodite was simulated with an alkaline U-containing, high-carbonate tank waste solution that diffused into intragrain fractures, which originally contained Si-rich pore water in equilibrium with feldspar grains in the lithic fragments. The model was also used to simulate uranyl dissolution and release from contaminated sediment to recharge waters. With independently characterized parameters for Na-boltwoodite dissolution, the model simulations demonstrated that diffusion could significantly decrease the rates of intragrain uranyl mineral dissolution due to diffusion-induced local solubility limitation with respect to Na-boltwoodite.