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The Northern Gulf of Mexico hosts a severe dead zone, an oxygen-depleted area spanning 1,618,000 hectares, threatening over 40% of the U.S. fishing industry and causing annual losses of USD 82 million. Using a System Dynamics (SD) approach, this study examined the Mississippi–Atchafalaya River Basin (MARB), a major contributor to hypoxia in the Gulf. A dynamic model, developed with Vensim software version 10.2.1 andexisting data, represented the physical, biological, and chemical processes leading to eutrophication and simulated dead zone formation over time. Various policies were assessed, considering natural system variability. The findings showed that focusing solely on nitrogen control reduced the dead zone but required greater intensity or managing other inputs to meet environmental goals. Runoff control policies delayed nutrient discharge but did not significantly alter long-term outcomes. Extreme condition tests highlighted the critical role of runoff dynamics, dependent on nitrogen load relative to flow volume from upstream. The model suggests interventions should not just reduce eutrophication inputs but enhance factors slowing down the process, allowing natural denitrification to override anthropogenic nitrification.