The transition zone between the Mu Us Sandy Land and the Loess Plateau is considered an ecologically fragile area. However, significant changes in land use have occurred in the past few decades due to changes in land policies and the implementation of major national ecological projects. Despite this, there is still a lack of clear investigation into the impact of these changes on the landscape structure and ecological health of the area. This study utilizes high-resolution annual land use data from China, along with multi-index models and algorithms, to comprehensively analyze regional land use changes, landscape patterns, and the ecological environment’s quality. Through a comprehensive analysis of various factors, including changes in quantity, transformation in land types, spatial dynamics, landscape structure, and ecological quality, we aim to provide a better understanding of the complex interactions between land use and ecological systems in this area. The research results indicate that: (1) Since 2000, 9057.4 km2 of land in the study area has undergone changes. The grassland area has the largest increase, the forest area has the fastest growth rate, while cropland and barren land have decreased to varying degrees, and impervious surface has slightly expanded. (2) The movement trajectory of the center of gravity for different land types is closely related to human activities such as land development and utilization, as well as ecological restoration. Land changes have resulted in an escalation of landscape fragmentation, a reduction in landscape diversity, and a decline in the uniform distribution of different types. (3) Ecological land is the key to improving the ecological environment. The increase in ecological land area in the study area has led to an improvement in the quality of the ecological environment. The net contribution rate of land change to ecological improvement reaches 1.99%. The analysis methods and perspectives used in this study can be applied to other similar studies. The study’s findings enhance the understanding of how land and vegetation changes affect the ecological environment in this crucial area. They are of great significance in guiding the development and utilization of land resources and the implementation of ecological environment projects.