The impact of land use type on the content of potentially toxic elements (PTEs) in the soils of the Qinghai-Tibet Plateau (QTP) and the associated ecological and human health risks has drawn great attention. Consequently, in this study, top- and subsurface soil samples were collected from areas with four different land uses (i.e., cropland, forest, grassland, and developed area) and the total contents of Cr, Cd, Cu, Pb and Zn were determined. Geostatistical analysis, self-organizing map (SOM), and positive matrix factorization (PMF), ecological risk assessment (ERA) and human health risk assessment (HRA) were applied and used to classify and identify the contamination sources and assess the potential risk. Partial least squares path modeling (PLS-PM) was applied to clarify the relationship of land use with PTE contents and risk. The PTE contents in all topsoil samples surpassed the respective background concentrations of China and corresponding subsurface concentrations. However, the ecological risk of all soil samples remained at a moderate or considerable level across the four land use types. Developed area and cropland showed a higher ecological risk than the other two land use types. Industrial discharges (32.8%), agricultural inputs (22.6%), natural sources (23.7%), and traffic emissions (20.9%) were the primary PTE sources in the tested soils, which indicate that anthropogenic activities have significantly affected soil PTE contents to a greater extent than other sources. Industrial discharge was the most prominent source of non-carcinogenic health risk, contributing 37.7% for adults and 35.2% for children of the total risk. The results of PLS-PM revealed that land use change associated with intensive human activities such as industrial activities and agricultural practices distinctly affected the PTE contents in soils of the Qinghai-Tibet Plateau.