Water resources play a key role in the development of regional economy and stability of ecosystem in the middle Loess Plateau, China. Spatial variability of fluoride (F−) and its geochemical control with other dissolved ions in the middle Loess Plateau were discussed. Samples were neutral to weak alkaline (pH = 7.4–9.6) with little variation of ion concentrations between river water and groundwater. The F− concentrations ranged from 0.2 to 3.1 mg/L, with an mean value of 0.9 mg/L. Approximately 31% of samples in northern and southern part of the study area were HCO3 −–Na+ water type with F− levels higher than the Chinese Drinking Water Standard of 1.0 mg/L. About 12% samples in the central part were HCO3 −–Ca2+ water type with F− content lesser than recommended value for caries control of 0.5 mg/L. The Quaternary deposits in the study area were the mainly F− sources of natural waters, and rainwater also contributed some F−. The alkaline characteristic of natural waters favored desorption of F− from hydrous metal oxides in loess, the climate of the study area, cation exchange, and CaCO3 precipitation further increased F− concentrations in natural waters in the middle Loess Plateau. Moreover, the chemical data analyzed in the principal component analysis (PCA) also indicated that climate coupled with geochemical processes was the main controlling factor for high F− in natural waters in the area. For the supply of high quality drinking water with safe F−, short-term and long-term action plans as well as awareness/education programs for the public were advocated.