Fluorosis is the most widespread and serious endemic disease in the abandoned Yellow River flooding delta of East China. One of the important causes of fluorosis is drinking high-fluorine groundwater. In this study, 313 groundwater samples were collected in the central part of the flooding delta to address the chemistry of high-fluoride groundwater, and 33 core samples were collected from one borehole of 150 m depth to analyse the vertical distribution characteristics of total fluorine and water-soluble fluorine. The fluorine concentration in groundwater ranges from 0.2 to 6.7 mg/L, and 72.8% of the samples have fluorine above the China maximum permissible limit of 1.0 mg/L for drinking water. These 313 samples can be divided into nine hydrochemical subtypes, and over 77% of the samples belong to the bicarbonate types. High-fluorine groundwater (over 3.0 mg/L) is generally alkaline water with high HCO₃⁻ and low Ca²⁺. The concentration of water-soluble fluorine decreases gradually with the increase of formation depth, and that in vertical sediment is negatively correlated with Ca²⁺ and Cl⁻, but positively correlated with HCO₃⁻. According to the calculation by PHREEQC package, MgF⁺ and CaF⁺ are the dominant species controlling the endemic fluorosis of the study area.