<p>Excessive groundwater abstraction from karst aquifers can alter the hydrodynamic conditions of karst systems, resulting in declining groundwater levels and intensified water–rock interactions. Intensified water–rock interactions may subsequently trigger geoenvironmental issues like deterioration in water quality. From the 1970s to the early 21st century, the increase in exploitation of karst groundwater resources in the Xiangshan karst region of Huaibei City, China, has continuously lowered groundwater levels and increased groundwater total dissolved solids (TDS) content. The objective of this study was to explore the spatiotemporal correlation between groundwater TDS concentrations and groundwater levels in karst aquifers using multivariate statistical techniques in the Xiangshan karst region. Results showed that TDS variations exhibited a time lag relative to the fluctuations of karst groundwater levels. The correlation between TDS concentrations and karst groundwater levels displayed three spatial patterns: (1) an negative correlation in the center of the study area with thin overburden, which coincided with the extent of the groundwater depression cone; (2) a slight correlation existed in the northern region where karst bedrock is exposed; and (3) a positive correlation evidenced by the variations in the southern region with thick overburden. Local indicators of spatial autocorrelation (BiLISA) analysis revealed four distinct clusters in different regions, indicating the influence of anthropogenic factors as well as natural factors. These results highlight that groundwater exploitation has direct consequences on the overall functioning of the karst aquifer, which disturbed not only the subsurface hydrodynamic equilibrium but also the hydrochemical steady state, thus causing changes in groundwater quality.</p>