Excessive nitrogen fertilization not only reduces nitrogen (N) use efficiency but also increases greenhouse emissions, posing environmental risks. Efficient utilization of N is crucial for cotton growth and fiber quality, particularly in saline-alkali soils where salinity limits nutrient uptake. A three-year field experiment was conducted in a typical arid region of North Western China to investigate the effects of six N application rates (0, 150, 250, 300, 350, 450 kg N & sdot;ha-1) and two water types (non-ionized saline water and ionized saline water) and their interactions on the growth, shoot dry matter (SDM), yield (Y), fiber quality and N-use efficiency of cotton (Gossypium hirsutum L.). The maximum leaf area index (LAI), absolute growth rate (AGR), photosynthetic rate, yield, fiber quality index (FQI) and water productivity (WP) significantly increased with the increase in application rate. Soil salinity accumulation in the 0-100 cm layer increased linearly with N rates, while salinity in the 0-40 cm layer first decreased and then increased. Soil enzyme activities measured in 2018 and 2019 showed that ionized saline water irrigation enhanced soil sucrase, urease, alkaline phosphatase, and catalase the cotton rhizosphere. Compared with the non-ionized saline water, the root biomass and root length of ionized saline water treatment significantly improved by 29.7 % and 16.6 %, respectively. A nitrogen application rate 300 kg N & sdot;ha-1 combined with ionized saline water is recommended as an effective fertilization strategy achieve high seed cotton yield (6997.9-8352.5 kg & sdot;ha-1), improved fiber quality, and maximum water productivity (12.0-14.5 kg & sdot;ha-1 & sdot;mm) and nitrogen use efficiency (15.6-18.6 kg & sdot;kg-1) for cotton. Our results provide new technical pathway for integrating saline water with nitrogen management to achieve high-quality and resource-efficient cotton production in arid regions.