Freshwater scarcity and soil salinization pose significant challenges to sustainable agriculture in arid and semiarid regions. To address these issues, a field experiment supported by theoretical analysis was conducted in a representative cotton-growing area in southern Xinjiang during April-September 2020 and 2021. The study evaluated the effects of magnetoelectrically activated brackish water combined with nitrogen management under plastic-mulched drip irrigation on soil salinization, nutrient availability, soil enzyme activities, and cotton yield. The experiment included two irrigation water qualities (freshwater, CK; brackish water, B), three water treatments (magnetized brackish water r, MB; de-electronic brackish water, DB; magnetoelectrically activated water, MDB), and six nitrogen levels (0, 150, 250, 300, 350, and 450 kg/ha), resulting in 30 treatment combinations. Compared with conventional brackish water, activated brackish water increased soil volumetric water content by 0.09%-21.22% and reduced salt accumulation in the 0-40 cm root zone by 0.09%-8.84%. Cotton nutrient uptake increased, leading to decreases in soil nutrient contents by 0.02%-68.98%, and soil enzyme activities were enhanced by 1.12%-36.52%. Under activated irrigation, seed cotton yield and yield components increased by -3.10%-31.39%, with the best performance observed under magnetoelectrically activated brackish water. Optimal water-nitrogen management strategies were also identified for different irrigation water qualities. Overall, these results indicate that the use of activated brackish water can improve soil conditions, enhance nutrient cycling, and support sustainable cotton production in arid regions.