Abstract: Drought and soil salinity are two major limiting factors of agricultural productivity in arid northwest China. Particularly in Xinjiang, among the 7.09 million hm² of cultivated land in Xinjiang, 2.96 million hm² of cultivated land is affected by saline-alkali damage to varying degrees, accounting for more than 40 %, which seriously affects land productivity. At the same time, the ratio of agricultural water to total water consumption is more than 90 %, saline water resources have great application potential, but the potential threat to soil secondary salinization is also worrying. However, the response mechanisms of soil water-salt dynamics and cotton growth to salt-drought stress remain unclear. To address above mentioned issues, we used Xinluzao 42, a conventional cotton variety widely grown in Xinjiang Province, as the test material. Additionally, a pot experiment was conducted using a three-factor (soil salinity, irrigation volume, and water salinity) and four-level orthogonal design, comprising 16 treatments: four initial soil salinity levels (T1: 2 g/kg, T2: 4 g/kg, T3: 6 g/kg, T4: 8 g/kg), four irrigation volumes (W1: 3375 m³/hm², W2: 3750 m³/hm², W3: 4125 m³/hm², W4: 4500 m³/hm²), and four irrigation water salinities (S1: 2 g/L, S2: 5 g/L, S3: 8 g/L, S4: 11 g/L) during 2022 in Shihezi, Xinjiang. We conducted a comparative study to investigate changes in soil water and salt content, growth and physiology of cotton, as well as seed cotton yield and fiber quality under combined salinity-drought stress in drip irrigation conditions, and their underlying relationships with soil water and salt environment with yield and fiber quality. Correlation analysis, structural equation modeling, and the entropy weight TOPSIS method were applied to comprehensively evaluate the effects of salt–drought stress on soil water–salt dynamics and cotton growth. The results showed that soil water content and salt concentration during different growth stages were linearly and positively correlated with initial soil salinity and irrigation water salinity, while they generally exhibited a quadratic relationship with irrigation quota, though patterns varied across growth stages. Salt–drought stress significantly reduced cotton growth, photosynthetic characteristics, yield, and water use efficiency (WUE), with the poorest performance observed under treatment T4W1S4, where yield and WUE were 924 kg/hm² and 0.274 kg/m³, respectively. The fiber quality index was lowest (8965.2) under T4W2S3. The highest plant height and leaf area index were observed in T3W3S1, stem diameter in T1W2S2, and photosynthetic rate, transpiration rate, and stomatal conductance in T4W3S2. The highest lint yield (5086 kg/hm²) occurred under T3W4S2, while T1W1S1 achieved the best WUE (10.314 kg/hm²·mm^-1) and fiber quality index (12,559.4). Salt–drought stress altered the soil water–salt environment, thereby affecting cotton growth and development. Specifically, the total effects of soil initial salinity and irrigation water salinity on cotton growth characteristics, photosynthetic characteristics, yield, water use efficiency, and fiber comprehensive quality index were all negative effects, while irrigation amount had positive effects on these five factors. Further, we adopted a comprehensive evaluation that identified the top three optimal treatments as T1W2S2, T1W1S1, and T2W2S1, however, the worst three treatments as T4W1S4, T3W2S4, and T4W2S3, respectively. These findings provide theoretical reference for stabilizing and increasing cotton yields in arid regions of Northwest China.