Land use profoundly changes the terrestrial ecosystem and landscape patterns, and these changes reveal the extent and scope of the ecological influence of land use on the terrestrial ecosystem. The study area selected for this research was the middle reaches of the Heihe River. Based on land use data (1986, 2000, and 2014), we proposed an ecological risk index of land use by combining a landscape disturbance index with a landscape fragility index. An exponential model was selected to perform kriging interpolation, as well as spatial autocorrelations and semivariance analyses which could reveal the spatial aggregation patterns. The results indicated that the ecological risk of the middle reaches of the Heihe River was generally high, and higher in the northwest. The high values of the ecological risk index (ERI) tended to decrease, and the low ERI values tended to increase. Positive spatial autocorrelations and a prominent scale-dependence were observed among the ERI values. The main hot areas with High-High local autocorrelations were located in the north, and the cold areas with low-low local autocorrelations were primarily located in the middle corridor plain and Qilian Mountains. From 1986 to 2014, low and relatively low ecological risk areas decreased while relatively high risk areas expanded. A middle level of ecological risk was observed in Ganzhou and Minle counties. Shandan County presented a serious polarization, with high ecological risk areas observed in the north and low ecological risk areas observed in the southern Shandan horse farm. In order to lower the eco-risk and achieve the sustainability of land use, these results suggest policies to strictly control the oasis expansion and the occupation of farmland for urbanization. Some inefficient farmland should transform into grassland in appropriate cases.