Perfluorinated compounds (PFCs) are organo-fluorine compounds which have been identified at significant levels in soils due to their widespread usage in industrial and commercial applications. However, few studies are available regarding the occurrence of PFCs in the environment of endemic fluorosis areas. To address the issue, soils collected from an endemic fluorosis area of southwestern China were analyzed for the distribution of fluorine and 21 kinds of PFCs. The average water-soluble fluorine concentration in cultivated soil (4.87 mg kg) was significantly higher than that in uncultivated soil (3.15 mg kg), which mainly ascribed to the utilization of fluorine-enriched fertilizers during agricultural practices. Concentrations of ΣPFCs in all soils ranged from 0.508 to 6.83 ng g, with an average of 2.81 ng g, dominated by perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA). Highest ΣPFCs was found in the soil samples collected from cropland with intensive agricultural activities. Long-chain PFCs, including four perfluoroalkylcarboxylic acids (PFCAs, C ≥ 8) and one perfluoroalkylsulfonic acids (PFSAs) (perfluorooctane sulfonate (PFOS), C8), exhibited high levels in soils, probably due to their higher hydrophobicity and lower water-solubility than short-chain PFCs. While in sediments, short-chain PFCAs were the dominant compounds. Based on correlation analysis, the relationship between total fluorine and PFCs was insignificant, and soil organic matter was a relevant factor affecting PFCs distribution in soils. This study is expected to present a more comprehensive information about fluorine contamination under the influence of agricultural activities in an endemic fluorosis area.