Gansu Province has rich and diverse landscape types, which play a key role in the ecological security of Western China, and also provide important material bases and ecological services for local development. Due to the impact of climate change and unsustainable human activities, the security and stability of the ecological environment in some areas of Gansu Province has become severely challenged. Based on the climate change initiative-land cover (CCI-LC) data of European Aviation Administration, this study analyzes the characteristics of land use and cover change in Gansu Province from 2005 to 2019, using a ‘dynamic degree and transfer matrix’ methodology. By constructing the landscape ecological risk index and using the spatial autocorrelation analysis method, this study analyzes the spatial distribution characteristics of landscape ecological risk. It was found that: 1) From 2005 to 2019, the area of bare land decreased the most, with a change over the 15-year study period of 1.88%, followed by cultivated land, with a decrease of 2.31%; grassland area increased the most, with a five-year change (an annual increase) of 1.83%, followed by construction land, with an increase of 191.08%. 2) Among all land use and cover categories, the extent of change for construction land was the highest, and the rate of change remained at a consistently high level throughout the study period. The period with the highest overall extent of change was 2010-2019. 3) The land use/cover transfer matrix was mainly comprised of the transfer in and transfer out of cultivated land, forest land, grassland and bare land, as well as the transfer in of other land types to construction land. 4) The overall ecological risk value in 2019 was significantly higher than in 2005. Among the risk categories, the ‘low-risk’ category had the largest area, and the most frequent occurrence of transformation. Areas designated ‘medium risk’ and ‘high risk’ were comparatively small, they all have exhibited different degrees of growth. 5) From 2005 to 2019, Moran’s I remained at a high level. This index was positively correlated with the spatial distribution of landscape ecological risk and had a strong aggregation effect. The purpose of this study is to provide a scientific basis for land use planning and ecological risk control in Northwest China.