<p>Arsenic poisoning induced by high-arsenic (As) groundwater is a critical environmental and geological issue worldwide. Existing studies have confirmed the presence of geogenic high-As groundwater on the Xizang Plateau, yet its spatial distribution and enrichment mechanisms remain poorly understood. To address this, 83 water samples (75 groundwater, 5 rivers, 3 hot springs) were collected across Xizang in August 2023 and December 2024. All samples were analyzed for hydrochemical analysis of trace elements (As, Fe, etc.), major ions (Ca²⁺, HCO₃⁻, SO₄²^-, etc.), and dissolved organic carbon (DOC). H-O-C-S isotopes were analyzed for selected samples. The results reveal that groundwater with As &gt; 100&#xa0;μg/L is predominantly located in the Ngari region. The groundwater is characterized as the Ca–HCO₃ type, primarily influenced by water-rock interactions. The pH values range from 7.18 to 9.24, indicating weakly alkaline conditions, with higher pH and redox potential observed in summer compared with winter. Seasonal variations show higher As concentrations but lower Fe levels in summer, where the weak As–Fe correlation suggests As release probably occurs via alkaline desorption, whereas the strong correlation in winter points to reductive dissolution likely being the dominant mechanism. The slope of the <i>δ</i>D–<i>δ</i>¹⁸O relationship is &lt; 8, indicating significant evaporation, which is more intense in summer. For samples with As &gt; 50&#xa0;μg/L, a negative correlation between As and <i>δ</i>¹³C_DIC indicates that microbial degradation of organic carbon facilitates As mobilization, whereas a positive correlation between As and <i>δ</i>³⁴S_SO₄ suggests that sulfate reduction could also enhance As release. Overall, the release of As in groundwater is closely linked to the aforementioned biogeochemical processes.</p>