In this paper we demonstrate that hyporheic exchange can be represented simply as a one-dimensional diffusion process, where the diffusivity decays exponentially with depth into the sediment bed. Based on a meta-analysis of 106 previously published laboratory measurements of hyporheic exchange (capturing a range of bed morphologies, hydraulic conditions, sediment properties, and experimental approaches) we find that the reference diffusivity and mixing length-scale are functions of the permeability Reynolds Number and Schmidt Number. These dimensionless numbers, in turn, can be estimated for a particular stream from the median grain size of the sediment bed and the stream’s depth, slope, and temperature. Application of these results to a seminal study of nitrate removal in 72 headwater streams across the United States, reveals: (1) streams draining urban and agricultural landscapes have a diminished capacity for in-stream and in-bed mixing along with smaller subsurface storage zones compared to streams draining reference landscapes; (2) under steady-state conditions nitrate uptake in the sediment bed is primarily biologically controlled; and (3) under transient conditions (e.g., spills or storms) physical transport processes are likely to influence nitrate removal rates as well. While further research is needed, the simplicity and extensibility of the framework described here should facilitate cross-disciplinary discussions and inform reach-scale studies of pollutant fate and transport and facilitate their scale-up to watersheds and beyond.