The hydrochemical properties of groundwater play a crucial role in crop growth and soil health, as well as the maintenance of irrigation equipment. To ensure suitable water quality for irrigation, the present study was conducted to evaluate the hydrochemical properties of irrigation groundwater in a typical agricultural region of Serbia. Groundwater was sampled at three monitoring locations in the Srem region in Republic of Serbia between 2011 and 2020. Examined parameters included electrical conductivity (EC), total dissolved salts (TDS), pH values, and the concentrations of cations (sodium (Na+), calcium (Ca2+), magnesium (Mg2+) and potassium (K+)) and anions (bicarbonate (HCO3−), chloride (Cl−), sulfate (SO42−), and nitrate (NO3−)). Further assessment was done using three classification systems; Nejgebauer’s, the US USSL, and the FAO classification. To obtain a more detailed assessment, additional indices were included, such as Soluble Sodium Percentage (SSP), Sodium Adsorption Ratio (SAR), Residual Sodium Carbonate (RSC), Permeability Index (PI), Kelly’s Ratio (KR), Magnesium Adsorption Ratio (MAR), and Total Hardness (TH). The PCA analysis detected that the concentration of K+, Ca2+, and Na+ in the irrigation water were lower in recent years, while the concentration of Cl− was higher. The cluster analysis grouped the parameters into three clusters; I—electroconductivity, II—dry residue and HCO3−, and III—other water parameters for all three monitoring localities. According to the applied classifications, the majority of underground water samples were suitable for irrigation. However, some samples fell out of the range of the first class, indicating the need for regular water quality monitoring. In light of climate changes that influence water deficiency, the urgent need for wise and sustainable water use implies the application of a comprehensive approach to irrigation water quality assessment, as shown in this study.