Groundwater plays a key role in supplying water for drinking water, irrigation water, and industry water in the northern China. Recently, the availability and quality of groundwater resources in the eastern Loess Plateau (Shanxi province) have a serious impact on the agriculture, industry, and domestic sectors. This paper investigates the spatiotemporal variations of chemical and stable isotope composition of groundwater, and provides important information for the research of controlling factors of groundwater hydrochemical distribution in Shanxi province during two seasons. About 95 groundwater samples were collected from two seasons and measured the content of major ions and stable isotope, pH values, and total dissolved solids (TDS). The results showed that groundwater samples were mildly alkaline. Among all the groundwater samples, the HCO₃⁻ and Na⁺ dominated the total mass of the anions and cations, respectively. Significant seasonal and spatial variations can be observed in the TDS, deuterium (δ²H), and oxygen (δ¹⁸O) in groundwater samples. More pronounced variations of the groundwater TDS appeared in the quick-flow season with the highest TDS concentration observed at the central region and lower TDS values appeared in the northern and southern Shanxi. The groundwater samples mainly belong to the (HCO₃⁻-Ca²⁺-Na⁺) type and the (HCO₃⁻-SO₄²⁻-Ca²⁺-Na⁺) type. Rock weathering is the key controlling factor for the chemical composition of groundwater. In addition, nitrogen pollution of groundwater caused by human input is more significant in river valley basins such as the Yuncheng Basin, Linfen Basin, and Changzhi Basin. The significant influence of surface water-groundwater interaction for the groundwater can be observed at the valley basin in the central part of the Shanxi Province. The interaction between surface water and groundwater in the Linfen basin is especially remarkable.