The construction and operation of the Three Gorges Reservoir and the cascade reservoirs upstream have significantly altered the processes of flow and sediment in the main and tributary channels of the Yangtze River. This has led to substantial adjustments in the riverbed through erosion and deposition, thereby impacting flood protection, water resource utilization, navigation, and the aquatic environment in the Yangtze River basin. In this study, prototype measurements were used to analyze the variations in runoff and sediment load in the main channel of the Yangtze River, as well as the changes and evolution of the riverbed. Mathematical modeling was done to predict the trends in reservoir sedimentation and riverbed adjustments. The results indicate that, apart from the significantly increased runoff and sediment load in the river source region (Zhimenda station) over the past two decades, there is no clear unidirectional trend of increasing or decreasing in the main and tributary annual runoff of the Yangtze River. However, the release of reservoir outflows undergoes significant changes throughout the year due to reservoir regulation. Suspended sediment load in the upper Yangtze River has been decreasing since the 1990s, especially after the operation of the Three Gorges Reservoir and the four cascade reservoirs in the lower reach of the Jinsha River. The factors influencing flow and sediment variations include mainly climate change and human activities such as reservoir operation and soil and water conservation. The significant changes in flow and sediment conditions have disrupted the original relative equilibrium state of the main channel of the Yangtze River, leading to riverbed adjustments. The river sections in the upper reach, located within reservoir areas, have shifted from erosional state under natural conditions to accumulative state, while the middle and lower reaches have transitioned from a relatively equilibrium state to a process dominated by erosion and reconstruction. Overall, the river regime in the reservoir area and downstream of the Three Gorges Dam remains relatively stable, but there have been adjustments in some local river sections, for example, in the curved sections, particularly in the sharply curved sections downstream of the Three Gorges Dam, where gradual or abrupt chute cutoff has occurred. In the foreseeable future, the river channel downstream of the Three Gorges Dam will remain in an unsaturated state regarding sediment transport. The process of river channel erosion will persist for a long time and have far‐reaching consequences. Some long straight sections, multiple bifurcation sections, and sections with large curvature are expected to undergo certain adjustments in the river regime, necessitating continuous observation, long‐term monitoring, and timely river management and channel governance.