The water and energy consumption characteristics of five crops (rice, corn, potato, rape and soybean) in Guizhou from 2010 to 2020 were analyzed using a water footprint and energy consumption accounting model based on relevant statistical data. Additionally, a multi-objective optimization model with constraints on water resources, energy, land, and food supply was developed to achieve optimal economic and ecological benefits, aiming to scientifically optimize the planting structure of five crops in Guizhou. The results showed: (1) there were significant differences in the water footprint and energy consumption per unit area of major crops in Guizhou during the period from 2010 to 2020. Specifically, rice, potato, soybean, corn, and rape were classified as extremely high water and energy-consuming crops, high water and energy-consuming crops, high water but medium energy-consuming crops, medium water and low energy-consuming crops, and low water and energy-consuming crops, respectively. (2) The water footprints of five crops were primarily dominated by green water consumption. Among them, rice, corn, and potato were the major contributors to the water footprint, accounting for 85% of the total. The energy consumption structure of five crops differed, with rice mainly consuming electricity, corn and potato mainly consuming chemical fertilizers, and rape and soybean primarily consuming fuel. Notably, rice and potato were the major contributors to the energy consumption, accounting for 69% of the total. (3) There were significant spatial variations in the crop planting structure in Guizhou due to differences in natural conditions. Specifically, rice was primarily distributed in the flat areas below 600m in altitude in southern Guizhou, corn was planted across the province but with varying qualities, potato was mainly cultivated in areas with altitudes ranging from 100 to 2900m, rape was primarily planted in central Guizhou, and soybean was cultivated in all regions with small differences in the proportion of each region. (4) After optimization, there was a slight decrease in the total planting area of five crops in Guizhou province. Notably, the planting area of rape and potato increased by 14000 and 146000ha respectively, resulting in their shares increasing by 0.6 and 1.6 percentage points, respectively. Conversely, the planting area of rice and corn decreased by 171000 and 386000ha, respectively, causing their shares to decrease by 0.3 and 1.5 percentage points, respectively. Following the optimization in Guizhou, there was a reduction in water footprint of 3.06 billion m³, a decrease in chemical fertilizer usage of 150 million tons, and a reduction in energy consumption of 2459000 GJ. Consequently, the ecological benefits have been significantly improved, while the economic benefits have remained stable. The optimized planting structure, based on the water-energy-food nexus, considers both economic and ecological benefits, exhibiting characteristics of low water consumption, low energy consumption, and low pollution. This further promotes the sustainable development of agriculture in Guizhou.