The accuracy prediction for the crop yield is conducive to the food security in regions and/or nations. To some extent, the prediction model for crop yields combining the crop mechanism model with statistical regression model (SRM) can improve the timeliness and robustness of the final yield prediction. In this study, the accumulated biomass (AB) simulated by the Agricultural Production Systems sIMulator (APSIM) model and multiple climate indices (e.g., climate suitability indices and extreme climate indices) were incorporated into SRM to predict the wheat yield in the North China Plain (NCP). The results showed that the prediction model based on the random forest (RF) algorithm outperformed the prediction models using other regression algorithms. The prediction for the wheat yield at SM (the period from the start of grain filling to the milky stage) based on RF can obtain a higher accuracy (r = 0.86, RMSE = 683 kg ha−1 and MAE = 498 kg ha−1). With the progression of wheat growth, the performances of yield prediction models improved gradually. The prediction of yield at FS (the period from flowering to the start of grain filling) can achieve higher precision and a longer lead time, which can be viewed as the optimum period providing the decent performance of the yield prediction and about one month’s lead time. In addition, the precision of the predicted yield for the irrigated sites was higher than that for the rainfed sites. The APSIM-simulated AB had an importance of above 30% for the last three prediction events, including FIF event (the period from floral initiation to flowering), FS event (the period from flowering to the start of grain filling) and SM event (the period from the start of grain filling to the milky stage), which ranked first in the prediction model. The climate suitability indices, with a higher rank for every prediction event, played an important role in the prediction model. The winter wheat yield in the NCP was seriously affected by the low temperature events before flowering, the high temperature events after flowering and water stress. We hope that the prediction model can be used to develop adaptation strategies to mitigate the negative effects of climate change on crop productivity and provide the data support for food security.