[Objective] The spatiotemporal evolution characteristics and attributes of land desertification in the middle and upper reaches of Yarlung Zangbo River were analyzed and identified to provide scientific support for ecological restoration and protection and promote a virtuous cycle of the ecosystem in this region. [Methods] An improved desertification difference index method based on the three-dimensional space of vegetation, surface reflectance, and soil moisture (NDVI-Albedo-Wet) were employed to analyze the spatiotemporal evolution of land desertification in the research area during 1990—2020. On this basis, attribute analysis of land desertification was conducted from the perspectives of temporal changes and spatial differentiation using principal component analysis and geographical detector methods, respectively. [Results] The total area of land desertification decreased from 3.48×10⁴ km² in 1990 to 1.67×10⁴ km² in 2020; however, the degree of land desertification increased in certain areas, particularly in the western part of the study area, such as Saga and Jilong, and the southeastern parts, such as Kangma and Qiongjie County. The spatial distribution of land desertification exhibited a strip-like pattern along the main river channel from west to east, being concentrated on gentle slopes, moderate slopes, grasslands, and unused land. During 1990—2020, the reversal of land desertification in the study area was primarily influenced by human activities, with the principal contributing factors accounting for 59.1% of the total reversal. The spatial differentiation of land desertification shifted from dependence on natural geographical factors, such as elevation and wind speed, in 1990, to the synergistic influence of multiple factors, including natural and socioeconomic factors, in 2020, with the impact of various driving factors on the spatial distribution of land desertification exhibiting dual-factor enhancement and non-linear increase. [Conclusion] The degree of land desertification in the middle and upper reaches of the Yarlung Zangbo River basin was alleviated between 1988 and 2020; however, local exacerbations persisted. Hence, further strengthening the ecological restoration of the source area and enhancing sand source management and vegetation cultivation within a 10 km radius of both the left and right banks of the river is necessary.