Natural Isotope Constraints on River Nitrate Sources in Polluted Regions

River nitrogen (N) pollution drives eutrophication and dead zones in more than two‐thirds of global estuaries and bays. Nitrate (NO 3 − ) is a highly mobile form of reactive N. Elevated NO 3 − concentrations in rivers deteriorate water quality and threaten aquatic biota and human health through toxic and carcinogenic effects. Mitigating river NO 3 − in polluted regions is pivotal to achieving Sustainable Development Goal 6 (SDG 6. Clean Water and Sanitation). However, the contributions of major sources to river NO 3 − loads remain poorly resolved, hindering ongoing mitigation efforts. Prevailing source apportionment models attribute river NO 3 − primarily to atmospheric deposition and agricultural non‐point sources. Here we establish a multi‐isotope mass‐balance framework that integrates natural N and oxygen isotopes ( δ 15 N, δ 18 O, Δ 17 O) with concentration, flux, and isotope effect pertaining to river NO 3 − sources, pools, and fates. Application of this framework to polluted rivers in Europe, Asia, and North America reveals that atmospheric deposition contributes only 5 ± 3%, non‐point sources account for 30 ± 9% (lower than previously reported >60%), wastewater remains a dominant contributor at 37 ± 8%, and previously neglected in‐stream nitrification contributes 28 ± 7%, effectively offsetting the fraction formerly overattributed to non‐point sources. This finding demonstrates the importance of strengthening wastewater treatment and controlling in‐river secondary NO 3 − production to reduce river NO 3 − pollution, and significantly advances our knowledge of river NO 3 − sources, which is essential for optimizing mitigation strategies to achieve SDG 6.