By selecting panel data from 2004 to 2018, this paper explores characteristics of tourism-economy-ecosystem spatio-temporal variations and trend prediction in Yangtze River Economic Belt with Vulnerability Research Method, Hot Spot Analysis, Spatial Variation Model, and Gray Prediction Model. Key research findings include: (1) from 2004 to 2018, the overall Vulnerability Index of the Yangtze River Economic Belt rose with fluctuations. Among all provinces and cities in China, the Vulnerability Index depressions are mainly in the eastern region, where the index is developing steadily; the peak value mainly occurs in the western region, with the index decreasing significantly. The spatial distribution of the overall sustainable development level from high to low is the eastern region, the central region and the western region, but the sustainable development level in the western region is likely to surpass that in the central region in the future. (2) The Vulnerability Index of the Yangtze River Economic Belt shows agglomeration expansion. The spatial and temporal distribution of hot spot analysis has changed significantly. The number of cold spots has decreased, while the number of hot spots has increased, which confirms that the value of vulnerability in the overall region is increasing. (3) The spatial differentiation characteristics of the Vulnerability Index in the Yangtze River Economic Belt have changed in different stages. The differentiation characteristics of "dispersion in the east and agglomeration in the west" have gradually been altered, and the overall index has presented a balanced development trend. (4) By predicting and calculating the regional Vulnerability Index of the Yangtze River Economic Belt from 2019 to 2023, it is found that the Vulnerability Index between 2019 and 2023 outperforms the index from 2014 to 2018. The development hidden danger caused by the high Vulnerability Index of the tourism-economy-ecosystem of the Yangtze River Economic Belt gradually became a realistic question which people must face to.