Reaches are a fundamental unit for lotic biogeochemical characterization, yet a functional classification of nutrient processing at the reach scale is currently lacking. Here, we introduce nutrient processing domains (NPDs) to integrate routing (nutrient delivery) and local (benthic uptake and transformation) processes that dictate longitudinal patterns of lotic biogeochemical function. An NPD is defined as a realm in functional space occupied by reaches that share similar biogeochemical character. Occupation of a given NPD reflects characteristic net material balance (NMB), exchange potential, and availability, associated with changes in solute load, the extent of hydrologic gain or loss, and changes in concentration from the head to the base of a reach, respectively. Using a mass-balance approach, we represent NMB as the effective solute flux (Feff, M L−2 T−1, where M = mass, L = length, and T = time), designating reaches as sources (+Feff) or sinks (−Feff). Discharge change along a reach is measured as the change in hydraulic load (ΔHL, L/T), reflecting the potential for import and export to influence solute loads. Finally, the ratio of downstream-to-upstream concentration (Cdwn:up) represents the net effect that processes have on nutrient availability. Using a 20-y historical record for N and P in the Upper Clark Fork River, Montana, USA, we employed this approach to 3 consecutive reaches covering nearly 90 km of channel length to address spatial and temporal dynamics in NPD behavior in a nutrient-rich, productive river system. For total N and total P, reaches typically occupied compiler or enhancer NPDs, displaying load increases without or with concomitant increases in concentration, respectively. In contrast, reaches were NO3− consumers, acting as sinks for NO3-N during summer and autumn. NO3− load reductions were typically accompanied by striking declines in concentration, despite positive exchange potential (i.e., +ΔHL). Measured Feff magnitudes for NO3− (−1.2 to −60.0 mg N m−2 d−1) were similar to those reported in the literature associated with autotrophic N demand. Individual reaches occupied contrasting NPDs for NO3-N and soluble reactive P by simultaneously serving as a sink for one and a source for the other. Hence, alternating reaches acted as enhancers or consumers, sequentially along the river, reflecting geologic and biological influences with implications for whole river behavior. The NPD approach combines routing influences of material exchange and local biological stream processes to provide a biogeochemical taxonomy for stream reaches with application to theory and practice.