Water, energy and food are fundamental resources for sustainable development. How to comprehensively evaluate the coupling and coordinated development of the water-energy-food system in the Yangtze River Economic Belt from temporal and spatial perspectives is very important for promoting the sustainable development of regional resources. Here, the water-energy-food system coupling coordination evaluation index system was constructed taking water, energy, food and the symbiotic units of water-energy, water-food and energy-food system as input units, each index was weighted by entropy method, and then the coupling coordination model and spatial autocorrelation analysis was used to quantitatively study the coordinated development of the water-energy-food system and the spatio-temporal dynamic characteristics of the Yangtze River Economic Belt from 2010 to 2019. The results show that the comprehensive evaluation index of the water-energy-food system in the Yangtze River Economic Belt showed a slow growth trend as a whole from 2010 to 2019, among which the water system contributed the most to the comprehensive evaluation index of the water-energy-food system, with an average annual contribution of 21.57%; the energy system contributed the least, which was only accounted for 11.95%. Whereas the coupling and coordination level of the water-energy-food system in the Yangtze River Economic Belt increased first then decreased, among which Sichuan Province increased by 5.05%, Chongqing City decreased by 2.83%, and the distribution presented significant spatial heterogeneity, with the upper reaches significantly higher than the middle and lower reaches. Among the units, energy resources was the weak point of water-energy-food system coupling and coordinated development. The coupling and coordination degree of water-energy-food system in the Yangtze River Economic Belt showed a significant spatial correlation, the high-high agglomerations distributed in the upper reaches, whereas the low-low agglomerations are mainly in the lower reaches. It is suggested that the provinces and cities in the Yangtze River Economic Belt should improve their resource management mechanisms according to local conditions, so as to promote the sustainable development of resources in the belt.