【Objective】In light of the shortage of water resources and the lower fertility and poor quality of soils in Xinjiang, this study explored the effects of varying irrigation volumes and ratios of organic to inorganic fertilizer application under aerated drip irrigation on the soil quality, cotton growth, yield, and water use efficiency of cotton fields. The objective was to provide a theoretical basis for determining an irrigation and fertilization model for cotton in Xinjiang that was water-saving, highly efficient, and sustainable. 【Method】Field experiments were conducted in the 146th Regiment area of the Xinjiang Production and Construction Corps in 2023 and 2024. Under aerated drip irrigation, two irrigation volumes (W1: 80%ETC and W2: 100%ETC, where ETC represents the crop evapotranspiration) and five ratios of organic to inorganic fertilizer application (OF1: 100% chemical fertilizer, OF2: 75% chemical fertilizer + 25% organic fertilizer, OF3: 50% chemical fertilizer + 50% organic fertilizer, OF4: 25% chemical fertilizer + 75% organic fertilizer, OF5: 100% organic fertilizer) were set up to study their impacts on the physical and chemical properties of soil quality, cotton growth including leaf area index (LAI), dry matter accumulation, yield, and water use efficiency (WUE). 【Result】The Soil Quality Index (SQI) increased with the rising proportion of organic fertilizer, showing an average increase of 9.9%-28.8% in the combined application of organic and inorganic fertilizers over the two years compared with the application of chemical fertilizer alone. Under deficit irrigation, soil moisture content, LAI, dry matter accumulation, and yield significantly decreased, while Water Use Efficiency (WUE) significantly increased. Under the two irrigation levels (W1 and W2), soil moisture content, cotton LAI, and dry matter accumulation first increased and then decreased as the proportion of organic fertilizer increased. Under W1, these indicators reached their maxima with the W1OF3 treatment, whereas under W2, their maxima were observed with the W2OF2 treatment. Compared with chemical fertilizer alone (OF1), the combined application of organic and inorganic fertilizers increased soil moisture content, LAI, and dry matter accumulation by 0.4%-5.2%, 4.1%-19.8%, and 3.7%-18.8% over two years, respectively. Over two years, the maximum seed cotton yield was observed under W2OF2 treatment, with an average yield of 6 739.99 kg·hm-2, but the highest WUE was achieved under the W1OF3 treatment, with an average value of 1.42 kg·m-3. The SQI, seed cotton yield, and WUE under different treatments were evaluated using the membership function method, TOPSIS method, and grey relational analysis, respectively. A comprehensive evaluation was carried out using an integrated differential combination evaluation model, determining the optimum treatment as W1OF3. 【Conclusion】Considering the priority of water-saving, while ensuring yield, and aiming to improve Water Use Efficiency (WUE) and soil quality, it was recommended that under aerated drip irrigation, applying 80% ETC for irrigation water volume and a combined application of 50% organic fertilizer and 50% chemical fertilizer, for serving as the optimal management measure for water-saving and efficient production in cotton fields in Xinjiang.