AbstractChina's food security has met standards set by the United Nations Food and Agriculture Organization. However, this development is based on excessive resource input and sacrificing the environment. There are few studies on how to evaluate food production systems with a sustainability framework. In order to guarantee the food security in Northwest China, and realize the sustainable development of agricultural production, this study was carried out. On the basis of comprehensive analysis of new problems faced, including water resources, cultivated land resources and ecological security, several indicators such as water resources development and utilization rate, cultivated land pressure index, cultivated land quality index, N and P emissions and emission intensity are proposed to comprehensively evaluate the sustainability of grain production in Northwest China and put forward countermeasures to realize regional sustainable development. The results show that the water resources are already at a high‐stress level as the development and utilization rate of water resources is 42.7% in 2015. Industrial and domestic water continues to squeeze agricultural water use (annual average reduction of 0.1%). The amount of per capita cultivated land in 2015 has decreased by 9.7% compared to 2000. The quality index of cultivated land is as low as 0.22. A series of ecological problems caused by agricultural production have intensified the ecological crisis in the Northwest, which in turn will further affect food security. Suggestions to address these issues include improving agricultural water use efficiency, strengthening the measures of arable land conservation, improving fertilizer utilization efficiency and reducing plastic‐film mulch residues.