Ecological sensitivity is an essential indicator for measuring the degree of ecological fragility of a region, and traditional highway routing ignores the ecological benefits of regional nature, which causes irreversible impacts on the natural environment. Based on the AHP method, this paper carries out a comprehensive assessment of the ecological sensitivity of the K0+000~K56+438 section of the Guanzhuang Tourist Highway in the Zhangjiajie Wuling Mountain Area from 2000 to 2020, and it utilizes the spatial autocorrelation analysis method to reveal the pattern of its spatial and temporal changes in ecological sensitivity. The following results were obtained. (1) The ecological condition of the study area is gradually improving, and the areas with higher sensitivity are mainly distributed in the northeast and southwest of the study area. (2) The ecological sensitivity of the study area has strong spatial autocorrelation, but the autocorrelation has been reduced in recent years, and the distribution of the ecological sensitivity has been gradually discretized. (3) There are problems of high ecological risk and construction difficulty in the traditional highway route selection scheme of the A line. The optimized route selection scheme, the K line, can effectively avoid highly sensitive areas by adjusting the route and bridge settings. Finally, the article proposes engineering construction suitability and ecological restoration strategies for different road sections regarding vegetation cover, landscape risk, and geological hazards. This study establishes a set of comprehensive technical chains for tourism highway routing in ecologically fragile areas based on the spatial and temporal evolution of sensitivity, which provides new ideas for traditional highway routing and is of great significance for maintaining the balance and stability of ecosystems within the road area.