To tackle the challenges of climate warming and freshwater scarcity, evaluating greenhouse gas (GHG) emissions and water demand in agricultural production can contribute positively to sustainable agricultural practices. This study aims to quantify the GHG emissions and water requirements of three major grains in diverse environmental regions in China, with a specific focus on exploring their spatial heterogeneity due to regional differences. The parameterized DNDC model was used to quantify crop GHG emissions, while the Penman-Monteith equation was utilized to assess crop water demand. The result showed that the total GHG emission of major grain in China was 372.43 Tg/yr (CO2), 11.68 Tg/yr (CH4), 475.56 Gg/yr (N2O) respectively; and the water demand was 473.60 Gm3, in 2015. The Middle-lower Yangtze Plain (MLYP) had the highest emission and water demand. High-temperature and high-precipitation regions had greater GHG emission intensity; the intensity of different GHG emissions was significantly influenced by the type of crops. Late rice had the highest emission intensity. The geospatial distribution of GHG emissions and water demand displayed opposite patterns, with meteorological conditions and crop types as the main reasons. Soil bulk density was the most significant soil element influencing regional emissions. These results will help to assess the spatial heterogeneity of agricultural “water and carbon”, and the quantitative results can be used as evaluation indicators to establish resource- and environment- friendly agricultural cropping patterns suitable for different cropping regions.