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The southwest karst area is considered to have the most vulnerable groundwater environment in China. Groundwater quality is an important factor restricting sustainable economic development. In this study, traditional water chemistry method, water quality index (WQI), and hazard index (HI) were applied to comparatively analyze the hydrochemical characteristics of groundwater and the water quality in the exposed karst region (EKR) and buried karst region (BKR) in Bama, a typical karst area in southwest China. Generally, the main water type was Ca/Mg–HCO 3. Due to the predominance of dissolution of carbonate rocks in EKR and silicate rocks in BKR, higher total dissolved solids (TDS), Ca and HCO 3 − concentrations, and lower H 2 SiO 3 content were detected in groundwater in EKR compared with BKR. As affected by weathering of rocks such as lead-zinc ore, the maximum concentrations of Zn and Sr were 11.23 mg/L and 13.30 mg/L, showing that mineral water resources are widely distributed in Bama. The ion ratios and isotope abundances (δD and δ18O) in groundwater samples indicated stronger evaporation and rock-water interaction in EKR than BKR. Human activities exerted a more significant influence on the water quality in EKR compared to BKR. The mean WQI value also suggested that the groundwater quality was better in BKR (9.56) than EKR (12.17). Although 95.7% of the water samples in the study area were classified as excellent based on their WQI values, 4.3% of the water samples still had significant health risks (HI > 1) due to the high Sb, Zn, As, and Sr concentrations. It is recommended to reduce anthropogenic pollution in EKR and develop a plan for clean production of mineral water industry according to local conditions, which will help the sustainable development of the local economy. [Display omitted] • Groundwater hydrochemistry in exposed and buried karst regions is totally different. • Aquatic environment in exposed karst regions is more sensitive than buried ones. • Sb, As, and Zn are the main trace elements which may pose non-carcinogenic risks. • Groundwater quality assessment contributes to sustainable water management. [ABSTRACT FROM AUTHOR]