This study assesses qualitative and quantitative changes in groundwater resources and their impact on land subsidence in Can Tho, Vietnam, from 2000 to 2018. Can Tho city is characterized by scarce water resources and intense industrial, domestic, agricultural, and mining usage, creating water stress. The vertical compaction rates and thus land subsidence, resulting from a head drawdown in three aquifers, were calculated using 1D consolidation of compressible porous media. Experiments were conducted in 16 wells clusters consisting of a total of 48 shallow and deep wells. The three wells from every 16 well clusters from different aquifers, namely the Middle-Upper Pleistocene confined aquifer (qp2-3), the Upper-Pleistocence (qp3), and a well in Holocene (qh), respectively, were examined. The Mann Kendal test with Sen’s slope was performed and for most of the wells, negative values of Kendall’s tau were found, which indicated decreasing trend of groundwater level. A significant change in groundwater level were also detected during the last eighteen years from 2000 to 2018. The results show significant downward trends of groundwater level for all of the wells of aquifer qp3 and qp2-3 except for a few shallow wells. The trend of this dropdown groundwater level for these deep wells is highly associated with extraction rates. The average subsidence rate of 4.28 cm yr􀀀 1 were observed in the study area. Tra Noc Industrial zones (QT8, QT16) showed a high subsidence rate which ranges from 5 to 7 cm yr􀀀 1. The calculated subsidence rates indicate the ongoing groundwater overexploitation, which might place Can Tho at risk of increased flooding and saltwater intrusion in the context of climate change and sea-level rise. The findings of this study call for effective policy strategies for sustainable water resource management to limit further land subsidence.