With the increasing scope and intensity of human activities, landscape ecological risk assessment has become an important means to predict and measure the quality and dynamic evolution of ecological environment. Taking Manas River Basin as the study area and selecting Landsat TM/ETM remote sensing images from 2000, 2005, 2010, and 2015, this paper used ENVI software to interpret the land use types and quantitatively analyzed the land use dynamic variation characteristics of the basin from 2000 to 2015. Based on the landscape pattern index, and the geo-statistical methods were used to explore the degree of landscape ecological risk and the characteristics of the spatial-temporal differentiation of the Manas River Basin. The results showed that: (1) From 2000 to 2015, the landscape pattern of the Manas River Basin has taken great changes. The area of cultivated land has increased the most (2638.31 km²), which mainly transformed from grassland and unutilized land. While the area of unutilized land has decreased the most (2559.99 km²), which mainly transformed into grassland, cultivated land and forest land. (2) The landscape ecological risk of the basin was divided into five grades. Within the period of this study, the regions with the lowest and medium levels of ecological risk have increased, whereas the regions with the higher and highest levels of ecological risk have decreased, and the whole landscape ecological risk index decreased. Thus, the ecological environment of the study area showed a trend of improvement on the whole. (3) The landscape risk distribution pattern of the Manas River Basin changed slightly during 2000-2005 and 2010-2015, but it changed significantly during 2005-2010. The main changes in the medium, higher and highest levels of ecological risk have dispersed and transferred to north and south of the study area, and the lowest level of ecological risk have transferred from south to north of the study area.