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Abstract: Skeletal fluorosis is a systemic chronic disease caused by long‐term intake of excessive fluoride, which accumulates in bone tissue and causes changes to the bone and periosteal tissue. Skeletal fluorosis is rarely considered in paleopathological analyses, but in areas with relatively high fluoride in the environment, it may be an important cause of bone hyperplasia. In this study, we observed pathological lesions consistent with fluorosis on two human skeletons from the Ming Dynasty (1368–1644 CE) excavated from a cemetery in western Henan Province. By using an electron microprobe to measure the fluoride content in the teeth, and by considering the living conditions in the area during the Ming Dynasty, we conclude that the remains show evidence of skeletal fluorosis. We also consider the content of fluoride in the local groundwater, the local way of life, and other factors, to identify potential causes of skeletal fluorosis in this population and demonstrate that environmental factors were the main cause. This offers insight into the relationship between humans and their environments in China, especially western Henan Province, in the historical past. It also demonstrates the unique contributions bioarchaeology can make to environmental health studies and studies of the history of health.