Abstract: In order to understand the main and interactive effects of water and nitrogen on crop growth and development, yield, fiber quality, and water-nitrogen use efficiency of mechanically harvested cotton with drip irrigation under plastic film in arid area of western Inner Mongolia, a two-factorial experiment with irrigation water amount and nitrogen dosage in completely randomized block design was conducted in Alxa Left Banner of Alxa League in Inner Mongolia. The levels of water irrigation were 216 mm (W₁), 288 mm (W₂) and 360 mm (W₃), and the nitrogen dosages were 127.5 kg·hm^-2(N₁), 195 kg·hm^-2(N₂) and 262.5 kg·hm^-2(N₃). The results showed that water was the decisive factor for cotton growth, and plant height and dry matter accumulation increased rapidly with increasing the water irrigation level, but the ratio of reproductive organs to shoot biomass decreased. Compared with the treatments W₁ and W₂, the average boll number per plant in W₃ was increased by 25.4% and 17.5%, the seed cotton yield was improved by 18.1% and 11.9%, but the single boll mass was decreased by 5.8% and 4.6%, respectively. It indicated that an increase in boll number per plant was the determining factor in achieving high seed cotton yield. Moreover, there was also a significant interactive effect between water and nitrogen affecting the seed cotton yield. Under the condition with low-level irrigation (W₁ and W₂), the highest seed cotton yield was measured in N₁; while for the condition in W₃, the seed cotton yield in N₂ was greater than that in N₁ and N₃ by 8.5% and 31.9%, respectively. In general, the regulation of water and nitrogen had no significant effect on fiber quality. Water use efficiencyin W₁N₁ was 1.37 kg·m^-3, which was not significantly different with the value in W₃N₂, and the nitrogen partial factor productivityin W₃N₁ was the maximum (51.35 kg·kg^-1). Therefore, irrigation had a significant effect on yield increasing, but nitrogen application promoted the seed cotton yield only under well-watered conditions. The treatment with irrigation amount of 360 mm and nitrogen fertilizer of 195 kg·hm^-2 could promote the shoot biomass accumulation significantly and achieve the highest seed cotton yield, and its water use efficiency and nitrogen partial factor productivity were 1.37 kg·m^-3 and 36.41 kg·kg^-1, respectively, indicating the potential of water-saving and yield increasing. Therefore, it was recommended as a suitable water and nitrogen management for the mechanically harvested cotton in arid area of western Inner Mongolia.