A model has been developed to investigate in-river sediment and phosphorus dynamics. This advective-dispersive model is coupled with hydrodynamics and sediment transport submodels to simulate suspended sediment, total dissolved phosphorus, total phosphorus, and particulate phosphorus concentrations under unsteady flow conditions. The model is applied to a 55-km stretch of the River Swale in Yorkshire, UK, within the framework of the generalized likelihood uncertainty estimation (GLUE) methodology. First, simulations are conducted without in-river interactions to separate the effects of the in-river dynamics from the observed data at the downstream end. Results show that there was relatively minimal sediment and phosphorus mass exchange between the overlying water and the riverbed during low flow periods and active mass exchange during storm events. Also, there was net phosphorus diffusion from the riverbed throughout the entire period and particulate phosphorus gain during storm events, indicating higher phosphorus concentration in the riverbed sediment. The second group of simulations is conducted with in-river interactions. The results show relatively strong simulation dependencies of particulate phosphorus and total phosphorus on both flow and suspended sediment. They indicate that the uncertainties of the flow and suspended sediment predictions considerably contribute to those in particulate phosphorus and total phosphorus predictions. However, the uncertainties of suspended sediment and total dissolved phosphorus predictions are already sufficient without including those propagated from the flow predictions. Finally, the results provide supporting evidence of a higher phosphorus concentration in the riverbed, which is obtained by assimilating all available data within the GLUE framework.