The Loess Plateau region is characterized by fragmented habitats and ecological vulnerability. Analyzing the changes in land use and ecological risk within the region is of great significance for promoting high-quality development of the Loess Plateau. The study utilized land use data from 2000, 2010, and 2020 in the Loess Plateau region to assess the spatio-temporal variation in land use patterns and landscape ecological risks, aiming to provide valuable references and decision support for ecological risk management and sustainable development in the area. The results indicated that the main land use types in the region are grassland and cropland. From 2000 to 2020, forest, grassland, and water areas increased by 1.39 × 106, 6.25 × 105, and 7.09 × 104 ha, respectively. The impervious area increased rapidly, growing from 9.77 × 104 ha in 2000 to 1.85 × 106 ha in 2020. The cropland decreased by 1.82 × 106 ha from 2000 to 2020, with 4.61 × 105, 4.95 × 106, and 8.91 × 105 ha of cropland converted to forest, grassland, and impervious area, respectively. The fragmentation of the ecological landscape in the region has decreased, and the diversity and richness of landscape types have increased. The fragmentation of cropland, forest, and grassland has decreased, and landscape patches have become more concentrated. High-value areas of landscape ecological risk in the region show a trend of continuous aggregation, altering the dispersion pattern of high-risk areas. Currently, high-risk areas of landscape ecology in the Loess Plateau region are mainly concentrated in northern Shaanxi and some areas along the Yellow River, such as Yulin, Yan’an, Ordos, and others. Currently, the ecological environment remains a bottleneck constraining the high-quality development of the Loess Plateau. It is necessary to persist in coordinated governance and ecological engineering construction, and improving the quality of ecological environment is a prerequisite for consolidating the social foundation and leading the high-quality development of the ecological industry on the Loess Plateau.