We investigate changes to in-stream nitrogen retention and metabolic processes in the Elbe River between 1978 and 2020. We analyzed multidecadal time series data and developed a metabolic nitrogen demand model to explain trends in dissolved inorganic nitrogen (DIN) retention, gross primary production (GPP), and ecosystem respiration (ER) during a period of highly dynamic pollution pressures in the Elbe River (central Europe). Our findings reveal a marked increase in summer DIN retention and a decrease in winter DIN retention, establishing a distinct seasonal pattern. We identified three distinct periods in the Elbe's DIN retention dynamics: dominantly heterotrophic under high organic and inorganic pollution pressure (1980-1990), transition (1990-2003), and dominantly autotrophic with lower pollution (2003-2017). We link these changes to reduced industrial pollution, improved wastewater treatment, and a shift in the in-stream balance between heterotrophic and autotrophic processes. During the first period, high ER caused elevated metabolic nitrogen demands, primarily driven by heterotrophic processes. As pollution from industrial and wastewater emissions decreased, GPP rates increased and ER gradually declined, prompting a shift towards an autotrophic-dominated nitrogen retention regime. Our study indicates tight coupling of nutrient reduction from external sources and dominant processes of natural attenuation in large rivers, which needs to be considered for projections of recovery trajectories for sustainable water quality.