The main flow migration in the middle Yangtze River occurs in most river sections and is affected by factors such as incoming water and sediment, riverbed boundaries, and channel shapes, leading to a complex riverbed evolution. Revealing the controlling factors and analyzing the developmental trends are important for addressing the adverse ecological impacts caused by these changes. Based on a large amount of observational data since the impoundment of the Three Gorges Reservoir, the characteristics of the main flow migration in the middle Yangtze River under different flow conditions were analyzed, and its correlation with the nodes and bars at the inlet, the plane shape of the river, and riverbed morphology were determined to identify the key controlling factors. The results showed that it is characterized by the displacement of the main flow zone during the middle-flow period. The key factors controlling the main flow migration include the deflecting action of the nodes and sidebars at the inlet, relaxation of the channel plane shape, and resistance difference caused by the riverbed morphology between the branches. The trend analysis suggests that the main flow migration in the middle Yangtze River may become more frequent after the operation of the cascade reservoirs in the future and may threaten the ecological environment.