Appropriate drip irrigation system uniformity can maintain a higher crop yield and reduce the initial investment of the system. In this study, investigating the optimal drip system uniformity for cotton, a two-dimensional soil water transport and crop growth coupling model was calibrated and validated by soil water dynamics, crop growth indices and cotton yield obtained from mulched drip irrigation field experiments in an arid region of Xinjiang Uygur Autonomous Region, China. The model performed well with the normalized root mean square error of 2.6-22.6% for soil moisture, 6.3-14.1% for leaf area index, 4.9-7.2% for above-ground biomass, and with the difference ranging from 2.5 to 8.2% for seed cotton yield (SCY). Next, SCYs were simulated under five Christiansen uniformity coefficients (CUs) of 55, 65, 75, 85 and 95% with three irrigation levels of 50, 75 and 100% full irrigation treatment. The predicted SCY was found to decrease as CU decreased under different irrigation treatments, and the more obvious effect of CU on SCY at 75 and 100% full irrigation treatment was obtained. In addition, SCY increased by 2.8-8.0% when CU increased from 55 to 75%, and increased by 0.1-4.6% when CU increased from 75 to 95%. Therefore, a target drip irrigation uniformity of CU=75% was recommended to obtain a higher cotton yield, while maintaining a lower installation cost in the arid region. Copyright (c) 2017 John Wiley & Sons, Ltd.