Aiming at the pollution and ecological hazards of the lake sediments of Bosten Lake, once China’s largest inland lake, the spatial distribution and influencing factors of the potentially-toxic elements in its surface sediments were studied with the methods of spatial autocorrelation, two-way cluster analysis, and redundancy analysis. Finally, based on the background value of potentially-toxic elements extracted from a sediment core, a comprehensive evaluation of the risk of these potentially-toxic elements was conducted with the potential-ecological-risk index and the pollution-load index. With data on the grain size, bulk-rock composition, and organic matter content, this comprehensive analysis suggested that with the enrichment of authigenic carbonate minerals, the content of potentially-toxic elements exhibited distinctive characteristics representative of arid regions with lower values than those in humid region. All potentially-toxic elements revealed a significant spatial autocorrelation, and high-value areas mainly occurred in the middle and southwest. The content of potentially-toxic elements is related to Al2O3, K2O, Fe2O3, TiO2, MgO, and MnO, and the storage medium of potentially-toxic elements mainly consists of small particles with a grain size <16 μm. The pollution load index (PLI) for the whole lake due to the potentially-toxic elements was 1.31, and the surface area with a PLI higher than 1 and a moderate pollution level accounted for 87.2% of the total lake area. The research conclusions have an important scientific value for future lake ecological quality assessment and lake environment governance.