Geogenic As enrichment is prevalent in freshwater systems worldwide, yet the connection between such enrichment and regional tectonics remains poorly understood, especially within orogenic environments like the Tibetan Plateau. To provide new insights into the sources and processes of arsenic, as well as its relationship with tectonics in the plateau basin, we selected the Yarlung Tsangpo basin, situated at the collision zone between the Indian (Himalaya block) and Eurasian plates (Lhasa block) as the study area. We analyzed and compared the chemical compositions of waters and sediments across various litho-tectonic domains. This also involved assessing arsenic concentrations in river waters, suspended particulate matter (SPM), sediments, geothermal waters, and rocks. The main findings are as follows: (a) High-arsenic geothermal waters and igneous rocks are common in the Lhasa block, and the discharge of these geothermal waters is the main source of dissolved As in river water, whereas erosion of igneous rocks contributes most of the As in sediments. (b) Metal oxides adsorb dissolved As, which leads to further As enrichment in the sediments. (c) The occurrence of high As concentrations in the southern Tibetan Plateau can be explained by a crustal cycling model. Arsenic likely originated in Neo-Tethys oceanic crustal rocks and was concentrated in the upper crust of the active continental margin (Lhasa block) during geological cycling at convergent plate boundaries. These studies highlight the role of tectonic settings on influencing arsenic enrichment in the plateau basin.