Human agriculture, wastewater, and use of fossil fuels have saturated ecosystems with nitrogen and phosphorus, threatening biodiversity and human water security at a global scale. Despite efforts to reduce nutrient pollution, carbon and nutrient concentrations have increased or remained high in many regions. Here, we applied a new ecohydrological framework to ~12,000 water samples collected by the U.S. Environmental Protection Agency from streams and lakes across the contiguous U.S. to identify spatial and temporal patterns in nutrient concentrations and leverage (an indicator of flux). For the contiguous U.S. and within ecoregions, we quantified trends for sites sampled repeatedly from 2000 to 2019, the persistence of spatial patterns over that period, and the patch size of nutrient sources and sinks. While we observed various temporal trends across ecoregions, the spatial patterns of nutrient and carbon concentrations in streams were persistent across and within ecoregions, potentially because of historical nutrient legacies, consistent nutrient sources, and inherent differences in nutrient removal capacity for various ecosystems. Watersheds showed strong critical source area dynamics in that 2-8% of the land area accounted for 75% of the estimated flux. Variability in nutrient contribution was greatest in catchments smaller than 250 km2 for most parameters. An ensemble of four machine learning models confirmed previously observed relationships between nutrient concentrations and a combination of land use and land cover, demonstrating how human activity and inherent nutrient removal capacity interactively determine nutrient balance. These findings suggest that targeted nutrient interventions in a small portion of the landscape could substantially improve water quality at continental scales. We recommend a dual approach of first prioritizing the reduction of nutrient inputs in catchments that exert disproportionate influence on downstream water chemistry, and second, enhancing nutrient removal capacity by restoring hydrological connectivity both laterally and vertically in stream networks.