Abstract: The oversupply of nitrogen fertilizers has caused serious environmental problems, such as water pollution, destruction of soil structure, and global warming. Thus, the optimal nitrogen application rate of winter wheat should consider the environmental impacts. Many attempts have been made to evaluate the optimal winter wheat nitrogen application rate using different indicators, such as yield, nitrogen use efficiency, and nitrogen uptake. However, previous studies have only focused on economic benefits and did not consider the ecological benefits. Furthermore, the optimal nitrogen application rates have been evaluated with individual indicators; a systematic approach that integrates these indicators has not yet been presented. To better understand the optimal nitrogen application rate for winter wheat under multi-objective constraints in the North China Plain, this study used the daily meteorological data, observation data of the phenology, and the yield of winter wheat at nine stations (Tangshan, Huanghua, Luancheng, Huimin, Nangong, Ganyu, Shangqiu, Zhumadian, and Shouxian) from 1981 to 2017, to simulate five indicators of the economic and environmental benefits of the winter wheat (yield, nitrogen partial factor productivity, nitrogen uptake, the balance between yield increase and nitrogen saving, and environmental-economic benefits) by using the crop estimation through resource and environment synthesis (CERES)-Wheat model. The relationship between each indicator and the nitrogen application rate was investigated to determine the optimal nitrogen application rates under different constraints. Finally, the comprehensive optimal nitrogen application rate was determined according to the economic and ecological benefits. The results indicated that the optimal nitrogen application rates varied across stations and objective constraints. The average value of the optimal nitrogen application rate for the nine stations from high to low were that constrained by nitrogen uptake (363 kg∙hm⁻²), yield (257 kg∙hm⁻²), environment-economic benefits (190 kg∙hm⁻²), the balance between yield increase and nitrogen saving (173 kg∙hm⁻²) and nitrogen partial factor productivity (30 kg∙hm⁻²). The optimal nitrogen application rates under the constraints of the balance between yield increase and nitrogen-saving and environmental-economic benefits were 173 kg∙hm⁻² and 190 kg∙hm⁻², respectively. This indicates a reduction by approximately 20%−30% of the nitrogen application rates for constraints related to yield maximization, and reductions by 47% and 42% compared to the actual nitrogen application rates of farmers in the North China Plain. Thus, the environmental damage caused by nitrogen fertilizers can be minimized under these constraints. Meanwhile, approximately 90% of the wheat yield can be obtained with these optimal nitrogen application rates, and economic and ecological benefits can be simultaneously guaranteed. To secure grain production and minimize environmental impacts, the optimal nitrogen application rates under the constraints of the balance between yield increase and nitrogen-saving and environmental-economic benefits can be regarded as the regional reference for winter wheat planting in the North China Plain. The regional reference of the optimal nitrogen application rates for winter wheat varied with zones, it was 150 kg∙hm⁻² in the piedmont plains of Taihang Mountain and Yanshan Mountain, and 170 kg∙hm⁻² in the Nanyang Basin. For the winter wheat in the Shandong Peninsula and the plains around Bohai Sea, the optimal nitrogen application rate was higher (200 kg∙hm⁻²), and in the Haihe Plain, the optimal nitrogen application rate was 225 kg∙hm⁻².