Long-term (>4 months) column experiments were performed to investigate the kinetics of uranyl (U(VI)) desorption in sediments collected from the Integrated Field Research Challenge site at the U.S. Department of Energy Hanford 300 Area. The experimental results were used to evaluate alternative multirate surface complexation reaction (MRSCR) approaches to describe the short and long-term kinetics of U(VI) desorption under flow conditions. The surface complexation reaction (SCR) stoichiometry and equilibrium constants and multirate parameters in the MRSCR models were independently characterized in batch and stirred flow-cell reactors. MRSCR models that were either additively constructed using the MRSCRs for individual size fractions, or composite in nature, could effectively describe short-term U(VI) desorption under flow conditions. The long-term desorption results, however, revealed that using the labile U concentration measured by carbonate extraction underestimated desorbable U(VI) and the long-term rate of U(VI) desorption. This study also found that the gravel size fraction (2–8 mm), which is typically treated as nonreactive in modeling U(VI) reactive transport because of low external surface area, can have an important effect on the U(VI) desorption in the sediment. This study demonstrates an approach to effectively extrapolate U(VI) desorption kinetics for field-scale application and identifies important parameters and uncertainties affecting model predictions.