The rich biodiversity in the floodplain area is influenced by both floodplain floods and groundwater (GW). To protect the ecological environment in the floodplain area, it is essential to study the interaction between floodplain floods and GW. The objective of this paper is to propose a coupling strategy between a hydrodynamic model and a GW model to provide an accurate simulation tool for quantifying the interaction between floodplain floods and GW. The case study is conducted in the floodplain area of the middle reaches of the Irtysh River in northwest China. Firstly, a two-dimensional hydrodynamic model based on TELEMAC-2D is constructed to accurately simulate floodplain floods under wetting and drying conditions. Secondly, a GW model based on MODFLOW is developed. Finally, a coupling strategy is proposed to achieve accurate and efficient integration between the hydrodynamic model and the GW model. The calibration and verification results of the model demonstrate high accuracy, with root mean squared error (RMSE) values of 0.51 m and 0.77 m between observed and calculated GW levels for the hydrodynamic–GW coupled model. The water balance results indicate that floodplain floods serve as the largest GW recharge source in the study area, while phreatic evaporation is the primary GW discharge item. This paper represents a novel attempt to couple a two-dimensional hydrodynamic model with a GW model. The research results provide a scientific tool for the ecological restoration of floodplain areas considering both surface water and GW, as well as the comprehensive management and regulation of wetland water resources and the water environment.