The synergistic regulation of the water–energy–food nexus in irrigation districts is important for promoting the sustainable management of agricultural resources in irrigation districts. In this paper, a new integrated optimization–evaluation modelling framework for the water–energy–food nexus in agricultural irrigation areas is developed. It can measure the synergistic effects of economic, social and environmental multidimensional objectives on the sustainable management of agricultural resources in irrigation areas. The model couples an optimisation module and an evaluation module, combines a multiobjective nonlinear planning model with an opportunity-constrained planning model and uses an entropy-weighted TOPSIS assessment approach to sustainably assess the multidimensional indicators of the water–energy–food nexus in irrigation districts, with full consideration given to the effects of uncertainty in agricultural water and soil resources and social systems. The feasibility of the constructed model is verified through a study of the Jinxi irrigation district. The results show that compared to the actual area, the optimised surface water and groundwater availability increased by 23.5% and 22.7%; the optimised total area increased by 4%, whereas corn decreased by 40%, rice increased by 34.6% and soybean decreased by 33.8%; the energy consumption decreased by 17.6% and the total recycled resources amounted to 8.97 × 109 kg, with a combined net economic benefit of CNY 1.25 × 109 more than the actual current amount. The synergistic development of the water–energy–food nexus (WEFN) in the district is relatively harmonious, suggesting that the district should focus on developing agricultural mechanisation and balancing economic benefits with environmental and ecological protection; furthermore, the model constructed should provide decision-making support for the efficient use of agricultural resources in the irrigation district.