Abstract: In response to the insufficient research on the spatio-temporal evolution, topographic gradient distribution, and driving factors of land use in typical agricultural and pastoral areas of the southern Qinghai-Tibet Plateau, in this study we employed GIS techniques, topographic gradient classification, and the PLUS model to address these gaps. Based on high-precision land cover data from 1985 to 2020, we systematically analyzed the distribution characteristics and change patterns of land use in the "One River and Two Tributaries" region of Tibet (the Yarlung Zangbo River and its Nyang and Lhasa tributaries) from spatio-temporal, county-level, and topographic gradient perspectives, and explored the driving mechanisms. The results indicated that: ① From 1985 to 2020, grassland and unused land dominated land use in the study area, with grassland showing a decreasing trend and other land use types expanding.② Cultivated land, water bodies, and construction land were highly concentrated in densely populated, low- to medium-elevation flat river valleys; forest land, grassland, and unused land were primarily distributed in undulating mountainous areas at medium to high elevations.③ Slope was the dominant factor driving changes in cultivated land and water bodies, with contribution degrees of 0.13 and 0.14, respectively; elevation was the dominant factor for changes in forest land, grassland, and unused land, with contribution degrees of 0.15, 0.11, and 0.14, respectively; population density was the dominant factor for construction land change (contribution degree of 0.26). Land use changes in the study area are profoundly influenced by both natural and socio-economic factors. It is essential to implement land use planning tailored to local conditions to promote the harmonious development of human-land relationships in the region.