The western plain of the Nansihu Lake Basin (NLB) is an important agricultural economic zone in Shandong Province, where there is a high content of fluoride in soils. Studying the content and influencing factors of fluoride in soils is of great significance for the maintenance of regional eco-logical security and human health. This study takes the farmland soils in the west of NLB as the research focus and uses a method based on GIS and geostatistics to quantitatively analyze the spatial variation characteristics of soil total fluoride and water-soluble fluoride contents to draw a map showing their spatial distribution. The effects on the spatial distribution of soil total fluoride and water-soluble fluoride were analyzed from the aspects of geomorphological type, soil parent material (stratigraphic lithology), crop type, and groundwater fluoride concentration, among others, and the correlation between groundwater and soil fluoride contents was also analyzed. Our study results in the following findings: (1) The average content of total fluoride in topsoil in the study area is 652.8 mg/kg, the national background value is exceeded in 99.5% of the sampling sites, and the background value of Shandong Province is exceeded in 98.7% of the sampling sites. The average water-soluble fluoride is 15.2 mg/kg and exceeds 5.0 mg/kg in 94.3% of the sampling sites. Topsoils have high values of total fluoride and water-soluble fluoride. (2) The total fluoride and water-soluble fluoride in topsoils exhibit moderate spatial variability, indicating that their spatial distribution is the result of structural factors such as soil parent materials and man-made random factors such as fluorinated fertilizers. (3) In the 2 m vertical profile of shallow soils, total fluoride and water-soluble fluoride increase with the increase in soil viscosity, and the water-soluble fluoride has the characteristics of surface aggregation due to the influence of soil adsorption. Because fluoride ions as ligands are easily adsorbed and form fluoride complexes with other ions such as aluminum ions, the water-soluble fluoride shows the characteristics of surface aggregation and fractionation. (4) The analysis of influencing factors reveals that the lithology of Quaternary strata, geomorpho-logical types, and planting crop types have significant effects on the distribution of the total fluoride and water-soluble fluoride in the topsoils, and the distribution of the groundwater soluble fluoride in the topsoils is not related to that in groundwater. Our study provides data and technical support for improving both the soil environmental quality and water quality of the eastern route of the South-to-North Water Transfer Project, thus helping to promote the sustainable development of the social economy and ecological environment in the NLB.