Soil salinization and freshwater scarcity are among the primary constraints limiting sustainable agricultural development in arid and semi-arid regions. To improve irrigation water use efficiency and promote the rational utilization of brackish water resources, this study integrated field experiments with theoretical analysis in typical cotton fields in southern Xinjiang. It systematically investigated the effects of magnetic-electric activated brackish water applied via mulched drip irrigation on soil salinity distribution, cotton physiological growth parameters, yield and quality, and water-nitrogen use efficiency. The results demonstrated that: (1) Activated brackish water significantly reduced soil salinity in the cotton root zone, with decreases in root-zone salt content and total salt accumulation ranging from 9.46 % to 23.60 % and 3.42-50.91 %, respectively; (2) It markedly enhanced cotton growth and physiological performance, with improvements ranging from -4.35-55.15 % and 0.92-29.51 %, respectively; (3) Compared to untreated brackish water, the activated treatment increased seed cotton yield and water-nitrogen use efficiency by 1.52 %-58.91 % and 74.79 %-96.60 %, respectively; (4) Considering the synergistic effects of activated water and nitrogen application, the optimal management regime was identified as an irrigation quota of 4875 m3 /ha combined with a nitrogen application rate of 350 kg/ha. These findings provide a scientific basis for mitigating freshwater scarcity and controlling secondary soil salinization in saline-prone regions.