Increased loading of nitrogen (N) and phosphorus (P) from agricultural and urban intensification has led to severe degradation of inland and coastal waters. Lakes, reservoirs, and wetlands (lentic systems) retain these nutrients, thus regulating their delivery to downstream waters. While the processes controlling N and P retention are relatively well-known, there is a lack of quantitative understanding of how these processes manifest across spatial scales. We synthesized data from 600 lentic systems around the world to gain insight into the relationship between hydrologic and biogeochemical controls on nutrient retention. Our results indicate that the first-order reaction rate constant, k [T−1], is inversely proportional to the hydraulic residence time, τ [T], across 6 orders of magnitude in residence time for total N, total P, nitrate, and phosphate. We hypothesized that the consistency of the relationship points to a strong hydrologic control on biogeochemical processing, and validated our hypothesis using a sediment-water model that links major nutrient removal processes with system size. Finally, the k-τ relationships were upscaled to the landscape scale using a wetland size-frequency distribution. Results suggest that small wetlands play a disproportionately large role in landscape-scale nutrient processing—50% of nitrogen removal occurs in wetlands smaller than 102.5 m2 in our example. Thus, given the same loss in wetland area, the nutrient retention potential lost is greater when smaller wetlands are preferentially lost from the landscape. Our study highlights the need for a stronger focus on small lentic systems as major nutrient sinks in the landscape.