Abstract Agriculture plays an important role in global climate change. The interaction and efficiency of use of land, water, and energy in agricultural activities are the principal factors affecting greenhouse gas (GHG) emissions and food production. However, comprehensive analysis exploring the mechanism of the land–water–energy system in agricultural production remains lacking. This study developed such a framework based on regional agricultural GHG emissions by combining top-down analysis that considered cross-sectoral interactions with bottom-up analysis that addressed the context-specific conditions of resources and technology. We employed the proposed framework to analyze the interaction of land–water–energy and factors influencing agricultural GHG emissions and to explore mitigation measures based on a case study of the Sanjiang Plain (China). Results showed cropland on the Sanjiang Plain produced 1.8 million tonnes of protein and released 10.9 million tonnes of CO2eq in 2015 using 3.0 million ha of arable land, 12.1 billion m3 of water, and 100.4 PJ of energy. Owing to their high input of resources and flooded cultivation, rice fields produced 29% of total crop protein but consumed 51% of total crop water use, 43% of total crop energy use, and emitted 54% of total crop GHG (CO2eq). Structural adjustment through conversion of half the paddy fields into dryland crops (e.g., wheat) could mitigate GHG emissions by 18.8% in 2020 compared with the baseline scenario. However, such change would be almost impossible given the Sanjiang Plain is one of China’s most important rice-producing areas. If integrated technology improvements were adopted, e.g., advanced crop–soil nutrition management, groundwater protection measures, water-saving irrigation technology, and low-carbon energy technology, GHG emissions could be reduced by 23.9% without sacrificing food production. This study used the nexus approach to analyze agricultural GHG emissions, providing a framework for sustainable agricultural management and a reference for understanding the land–water–energy nexus.