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It is of great significance to explore the influences of climate change on crop phenology and yield of the rotation system of winter wheat and summer maize in the Huang-Huai-Hai Plain, a major grain production base in China, for guaranteeing the food security of China. The APSIM-Wheat and APSIM-Maize models (V 7.6) were calibrated and verified based on experimental data of multiple years and multiple sites, which were obtained based on literature review. Then, future meteorological data predicted by ten different global climate models (GCMs) in the CMIP6 dataset were used to drive the verified APSIM models to simulate the changes of phenology and yield of winter wheat and summer maize in the time periods of 2021—2060 (2040s) and 2061—2100 (2080s) under two greenhouse gas emission scenarios of SSP2-4.5 and SSP5-8.5. Based on the analyses with multiple linear regression and random forest model, the positive and negative effects of climatic factors and change of crop reproductive stage on crop yield were analyzed and their importance was clarified. The result showed that compared with the baseline period (1981—2020), the vegetative stage of winter wheat was shortened, the reproductive stage was prolonged, and wheat yield was increased. These changes were more obvious under the SSP5-8.5 than that under the SSP1-2.6 scenario. The vegetative and reproductive stages of summer maize were both shortened, and maize yield was increased. However, compared with SSP2-4.5, maize yield would be reduced under the SSP5-8.5 scenario. Compared with SSP2-4.5, the total growth period of winter wheat-summer maize rotation system was shortened, the annual yield was increased, and the proportion of winter wheat yield was increased under SSP5-8.5 scenario. In the future, winter wheat yield was mainly positively correlated with solar radiation, daily mean temperature, and cumulative precipitation during the whole growing season. However, the increase of daily mean temperature and cumulative precipitation was unfavorable to yield increase in 2080s under the SSP5-8.5 scenario. Summer maize experienced the similar changes as winter wheat under future climate change, but daily mean temperature had a negative effect on maize yield. Based on the random forest model, the length of winter wheat reproductive stage and accumulated precipitation in the whole growing season had the greatest impacts on winter wheat yield. At the same time, CO2 concentration, daily average temperature, and accumulated precipitation in the whole growing season had the greatest impacts on summer maize yield. Future climate change would prolong winter wheat reproductive stage and shorten summer maize reproductive stage, but increase winter wheat and summer maize yields in the Huang-Huai-Hai Plain. However, the positive effects of temperature and precipitation on crop yield would become negative over time, resulting in a reduction of summer maize yield in 2080s under the SSP5-8.5 scenario. In general, crop yield mainly would depend on the synergistic effect of climate change and the change of crop growing stage. The results would provide a scientific base and theoretical guidance for the management and the adaption to future climate change of the rotation system of winter wheat and summer maize in the Huang-Huai-Hai Plain of China.