Irrigated agriculture has important implications for achieving the United Nations Sustainable Development Goals. However, there is a lack of systematic and quantitative analyses of its impacts on food-energy-water-CO2 nexus. Here we studied impacts of irrigated agriculture on food-energy-water- CO2 nexus across food sending systems [the North China Plain (NCP)], food receiving systems and spillover systems (Hubei Province, affected by interactions between sending and receiving systems), using life cycle assessment, model scenarios, and the framework of metacoupling (socioeconomic-environmental interactions within and across borders). Results indicated that food supply from the NCP promoted food sustainability in the rest of China, but the NCP consumed over four times more water than its total annual renewable water, with large variations in food-energy-water-CO2 nexus across counties. Although Hubei Province was seldom directly involved in the food trade, it experienced substantial losses in water and land due to the construction of the South-to-North Water Transfer Project which aims to alleviate water shortages in the NCP. This study suggests the need to understand impacts of agriculture on food-energy-water-CO2 nexus in other parts of the world to achieve global sustainability.