This study applied a comprehensive quantitative approach including statistical, principal component and gray relation analyses to assess the groundwater chemistry based on monitored data from 840 samples collected from the lower reaches of Tarim River from 2000 to 2009. The main findings were: (1) there were six types of groundwater chemistry in the lower reaches of Tarim River where Cl·SO4–Na·Mg was the dominant type accounting for 73.57% in all samples. There were linear relationships among chemical parameters, where TDS had significant multiple correlations with Na+, K+, Mg2+, Ca2+ and Cl−, respectively. (2) Three principal components (PC1, PC2 and PC3) were extracted. They included comprehensive measurements for salinization, alkalinity and pH, respectively. Most parameters showed decreasing trends during the period of 2000–2009, as well as the scores on PC1, because the concentrations of various chemical substances were diluted due to the uplift of the groundwater table in the lower reaches and the implementation of the ecological water delivery project in 2000. (3) HCO3− was the most sensitive chemical parameter affected by the groundwater table followed by TA, Mg2+, TH, SO42−, K+, TDS and TS. PC2 was the most sensitive principal component to the change of the groundwater table followed by PC1 and PC3.