The scientific evaluation of the eco-environmental impacts of transportation infrastructure constitutes a hot research topic today. Numerous studies have emphasized how land-based transportation infrastructure profoundly alters ecosystem structures and functions, particularly in ecologically fragile regions. As the world's highest and longest plateau railway, this region serves as an exemplary case study for elucidating the ecological ramifications of road construction and operation. Using a landscape ecological risk index, this study investigated the spatio-temporal patterns of landscape ecological risk along the Golmud-Lhasa section of the Qinghai-Tibet Railway from 1990 to 2020 according to land use, remote sensing, meteorological, topographic, and socioeconomic data. Subsequently, the underlying driving forces were analyzed utilizing the optimal parameters-based geographical Geodetector model. The results showed an overall low landscape ecological risk along the Golmud-Lhasa section of the Qinghai-Tibet Railway, and the highest, moderate, and lowest risk in the northeast, middle, and southwest regions, respectively. Meanwhile, the closer to the railway centerline, the higher the landscape ecological risk, particularly in urban areas. The landscape ecological risk increased slightly after the construction of the railway, with the risk index increasing from 0.29 to 0.30, with a growth rate of approximately 0.40%/a, with the expansion pattern displaying point- and axis-aligned characteristics. Moreover, the increasing trend of landscape ecological risk is particularly pronounced in the northeastern, southwestern edge, and central regions. Simultaneously, the urban and non-urban areas overall showed a decreasing and an increasing trend in risk, respectively. The landscape ecological risk was mainly controlled by vegetation cover, precipitation, and elevation (q>0.44), followed by temperature, economic development, and population density (q>0.13). The interaction of vegetation cover with elevation and temperature had the highest explanatory power (q>0.61). Though the socio-economic factors are secondary to the natural factors, their contributions increased during the operation period as characterized by a rise of the explanatory power by economic development and nighttime lights. These together indicate that the ecological risk along the Qinghai-Tibet Railway has been accelerated by increasing human activities during the construction and operation periods. The study's insights are pivotal for comprehending the ecological impacts of terrestrial transportation systems and formulating road construction strategies in China to mitigate adverse ecological effects, especially in ecologically fragile and sensitive areas. We recommend establishing ecological buffer zones along the route to promote ecological restoration and protection, alongside the implementation of a robust ecological environment monitoring system to regulate and intervene in potential ecological risks, thereby maintaining the ecological barrier status of the Qinghai-Tibet Plateau region.