The quantity of available water resources has been recognized as the key limiting factor for development of most of the arid regions. This paper focuses on the simulation–optimization for conjunctive use of surface water and groundwater on a large scale. In this study, Hetao Irrigation District in China, one of the largest irrigation districts in the Yellow River basin, is selected as a representative study area. The conjunctive management model of water resources is developed by means of dynamically coupling a large-scale hydrological model with an optimal allocation model. A groundwater level is adopted in the coupled model as the constraint condition and the optimal conjunctive utilization quantity of surface water and groundwater is set as the objective function. Finally, the coupled model is applied to calculate the optimal water supply quantity of surface water and groundwater and sustainable utilization scheme of water resources for 2020 and 2030 in Hetao Irrigation District. The modeling results demonstrate the conjunctive management model of water resources is an effective tool for appraising water resources in large-scale arid regions.