Abstract: Clarifying the spatial consistency between tourism eco-efficiency and regional eco-security can provide new ideas for the study of tourism ecological value. In this paper, the prefecture-level cities in the Middle Reaches of the Yangtze River from 2005 to 2018 were used as the research area. Single index method, PSR model and spatial consistency coefficient were used to evaluate tourism eco-efficiency, regional eco-security and their spatial consistency. Spatial analysis was used to study the spatio-temporal differentiation characteristics of tourism eco-efficiency, regional eco-security and their spatial consistency. Logistic and Probit models are used to explore the influencing factors. The results show that: (1) During the study period, the tourism eco-efficiency and regional eco-security in the Middle Reaches of the Yangtze River showed an upward trend. (2) The distance between the center of gravity of the two groups was from close to far, which indicates that there was an “inverted U-shaped” trend between them. (3) The number of equilibrium regions increased, while the number of non-equilibrium regions decreased. The spatial agglomeration intensity of the two types showed an increasing trend. (4) The equilibrium types of spatial consistency were positively affected by resource endowment, social security and environmental construction, while negatively affected by population, per capita basic living standards and scientific and technological progress. (5) The non-equilibrium types of spatial consistency were positively affected by per capita basic living standard, scientific and technological progress, industrial structure and environmental pollution, while negatively affected by social security, economic growth and environmental construction.