Potentially toxic elements (PTEs) in surface water in arid areas pose a serious threat to environmental safety and human health within a basin. It is important to determine the factors controlling PTEs and to assess the likelihood that they will pose a risk to human health in order to support the development of environmental protection and risk management strategies. In this study, a structural equation model and Bayesian method were combined to discuss the distribution and probabilistic health risks of PTEs in surface water in arid area, and the Tarim River Basin was taken as a case study. The results show that the average concentrations of As, Co, Cu, and Ni in the surface water in the Tarim River Basin ranged from 0.04 to 2.92 μg/L, which do not exceed the international standard values. However, the maximum value of As (19.20 μg/L) exceeded both the recommended drinking water standards and the Chinese irrigation water standards. Spatially, the high As concentrations were distributed in the upper reaches of the Kashgar River, and the high Co, Cu and Ni concentrations were distributed in reservoirs and lakes on the main stream of the Tarim River. The concentrations of the PTEs in the surface water in the basin were not only affected by random anthropogenic factors such as traffic discharge, agricultural activities and mining industry, but were also directly and indirectly influenced by climatic factors. The results of the probabilistic health risk assessment showed that the 95th percentile the total hazard index for infants exceeded the allowable value of 1, and the total carcinogenic risk of PTEs exposure in four age groups was at the notable level. In this study, we conducted a comprehensive analysis of the controlling factors and health risks associated with PTEs in surface water in the Tarim River Basin, and the findings are expected to provide a scientific basis for regional water environment management and safety control.