The interaction between a river and the sea results in a turbidity maximum zone (TMZ) within the estuary, which has a great impact on the local ecosystem. In the Yangtze River Estuary, the magnitude and extent of the TMZ vary with water discharge. In this study, the cumulative human activity altered the water discharge regime from the river to the estuary. In the post-Three Gorges Dam (TGD) period, water discharge increased by 35.10 % at Datong in February compared with that in the pre-TGD period. The effects of water discharge variation on the characteristics of the TMZ were analyzed during spring and neap tidal periods using the three-dimensional environmental fluid dynamic code (EFDC) model. The area of the TMZ decreased by 3.11 and 17.39 % during neap and spring tides, respectively. In addition, the upper limit of the TMZ moved 11.68 km seaward during neap tide, whereas the upper limit of the TMZ in the upstream and downstream areas moved seaward 9.65 and 2.34 km, respectively, during spring tide. These findings suggest that the area and location of the TMZ are more sensitive to upstream runoff during spring tide than during neap tide. These changes in the TMZ will impact the biochemical processes in the Yangtze River Estuary. In the foreseeable future, the distribution characteristic of TMZ will inevitably change due to variations in the Yangtze River discharge resulting from new human activities (i.e., new dams), which are being constructed upstream in the Yangtze River system.