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The middle and lower reaches of the Yangtze River (MLYR) plain represent the second-largest wheat producing area in China; the winter wheat-rice system is one of the main planting systems in this region. The use of the agricultural production system simulator (APSIM)-wheat model to simulate wheat production potential and evaluate the impact of future climate change on wheat production in this region is of great importance. In this study, the adaptability of the APSIM-wheat model in the MLYR was evaluated based on observational data collected in field experiments and daily meteorological data from experimental stations in Wuhan, Jingmen, and Xiangyang in Hubei province. The results showed significant positive relationships between model-predicted wheat growth duration from sowing to anthesis and maturity and the observed values, with coefficients of determination (R2) in ranges of 0.90–0.97 and 0.93–0.96, respectively. The normalized root-mean-square error (NRMSE) of the simulated growth durations and measured values were lower than 1.6%, and the refined index of agreement (dr-values) was in the range of 0.74–0.87. The percent mean absolute relative error (PMARE) was cited here as a new index, with a value below 1.4%, indicating that the model's rating was excellent. The model's performance in terms of grain yield and above-ground biomass simulation was also acceptable, although it was not as good as the growth periods simulation. The R2 value was higher than 0.75 and 0.72 for the simulation of grain yield and biomass, respectively. The indices NRMSE and PMARE were lower than 19.8% and 19.9%, and the dr-value was higher than 0.71. According to our results, APSIM-wheat was an effective and accurate model for simulating the phenology and yield production processes of wheat in the MLYR, and the results also provided a theoretical basis and technical support for further research on the yield potential of wheat-rice rotation planting systems with clarification of the key factors limiting the yield gap in this region. [ABSTRACT FROM AUTHOR]