Endemic fluorosis is widespread in China, especially in the arid and semi-arid areas of northwest China, where endemic fluorosis caused by consumption of drinking water high in fluorine content is very common. We analyzed data on endemic fluorosis collected in Ningxia, a typical high-fluorine area in the north of China. Fluorosis cases were identified in 539 villages in 1981, in 4449 villages in 2010, and in 3269 villages in 2017. These were located in 19 administrative counties. In 2017, a total of 1.07 million individuals suffered from fluorosis in Ningxia, with more children suffering from dental fluorosis and skeletal fluorosis. Among Qingshuihe River basin disease areas, the high incidence of endemic fluorosis is in Yuanzhou District and Xiji County of Guyuan City. The paper holds that the genesis of the high incidence of endemic fluorosis in Qingshui River basin is mainly caused by chemical weathering, evaporation and concentration, and dissolution of fluorine-containing rocks around the basin, which is also closely related to the semi-arid geographical region background, basin structure, groundwater chemical characteristics, and climatic conditions of the basin. The process of mutual recharge and transformation between Qingshui River and shallow groundwater in the basin is intense. There is a close coupling relationship between the power of central and southern Ningxia disease areas and Qingshui River watershed of excess fluorine water. Because the traditional drinking water source of the residents in the basin is shallow groundwater, the underground water is the main cause of the high incidence of endemic fluorosis. The results show that Xiji County and Yuanzhou District were the areas of high incidence of endemic fluorosis which gradually decreased to the middle and lower reaches of Qingshui River. In space, distribution characteristics are Qingshui River source area > Qingshui River valley basin area, tributary area > trunk stream area, upstream area > middle reaches area> downstream area of Qingshui River. This is relatively consistent with the spatial distribution of fluoride ion content in Qingshui River groundwater.