As the largest artesian irrigation area in northern China, the Hetao Plain is also one of the major grain-producing areas in China. Meanwhile, there is a large amount of highly mineralized groundwater resulting in the soil salinization and desertification in this region. In addition, this study also uses the traditional hydro-geochemical methods to investigate the spatial evolution characteristics and formation mechanisms of highly mineralized groundwater. The results indicate that there is a large amount of highly mineralized groundwater (salinity > 3 g/L) in the shallow aquifer over the Hetao Plain. As far as the spatial patterns are concerned, there are significant spatial differences. In accordance with the structural, paleogeographic, landform, and hydrogeological conditions, the highly mineralized groundwater in the Hetao Plain can be divided into five zones, namely, the front fan depression, the north bank of the Yellow River, Xishanzui, Hasuhai in the Hubao Plain, and Dalad banner on the south bank of the Yellow River. Among them, the highly mineralized groundwater of Xishanzui exhibits the largest value of the salinity > 10 g/L. The main cations are Mg2+ and Na+, while the main anions are Cl− and SO42−. Moreover, the groundwater in the highly mineralized area contains a large amount of I−. According to the analysis of Piper, Gibbs diagrams of groundwater, the proportion coefficients of various components and the indication of isotope, it can be seen that most of the chemical ions in groundwater in the highly mineralized zone come from evaporation-concentration, which are mainly affected by climate, sedimentary environment, hydrogeological conditions and hydrology. The source of high mineralization in Xishanzui are different from other high mineralization regions, and the highly mineralized groundwater in Xishanzui is formed by the infestation of deep underground salt brine. These results can provide scientific basis for the rational allocation of regional water resources and the promotion of water resources development and utilization.