Schistosomiasis is a severe public health problem in the Dongting Lake region, and its distribution, prevalence, and intensity of infection are particularly sensitive to environmental changes. In this study, the human and bovine schistosomiasis variations in the Dongting Lake region were studied from 1996 to 2010, and the relationships between schistosomiasis and water level were examined. Furthermore, based on these results, the potential effects of the Three Gorges Dam (TGD) on schistosomiasis were investigated. Results showed an increase in human schistosomiasis and in the scope of seriously affected regions, along with a decrease in bovine schistosomiasis. Human schistosomiasis was negatively correlated with water level during wet season (from May to October), particularly the average water level in October. This finding indicated that the decreasing water level may be highly related to the increasing of human schistosomiasis in the Dongting Lake region. Based on this result and the variation of schistosomiasis before and after the construction and operation of TGD, the impoundment of the Three Gorges reservoir is believed to decrease the water level and increase the contact between people and schistosomiasis. Therefore, the TGD, which is operated by regulating water and scheduling water operations, is not good for the control of human schistosomiasis in the Dongting Lake region. Although the extent of the influence of the TGD on schistosomiasis remains unclear, the influence of the TGD on preventing and controlling schistosomiasis should not be ignored.