Under intense human interference and extreme climate events, the flow-sediment regimes, deposition and erosion patterns, and river-lake interactions in the middle and lower reaches of the Yangtze River have undergone significant transformations. After the impoundment of the Three Gorges Project, the annual upstream sediment supply to the middle and lower Yangtze River has decreased by 70% to 93%, and the flow process has become more concentrated. However, the post-flood recession has accelerated due to the operation of cascade hydropower stations. The annual water supply from the four rivers and three outlets flowing into the Dongting Lake has shown no significant adjustments, with a decline of 9%, while the annual sediment supply has decreased significantly by 38%. The annual water and sediment supply of the five rivers into the Poyang Lake have decreased by 2% and 57%, respectively, while the annual water and sediment outflow from the Poyang Lake have increased by 1% and 5%, respectively. These adjustments have altered the deposition and erosion patterns in the middle and lower Yangtze River. To be specific, from 2003 to 2021, the cumulative erosion of the mainstream reached 5.03 billion m³, with an average annual erosion of 265 million m³per year. The deposition-erosion state of the Dongting Lake has shifted from being deposition-dominated to slight erosion-dominated, and the riverbed of the three outlets generally exhibits an erosion trend. Similarly, the deposition-erosion state of the Poyang Lake has changed from deposition to erosion, and the channel connecting the Poyang Lake to the mainstream Yangtze River shows severe erosion and down-cutting. A predictive model indicates that over the next three decades, the mainstream of the middle and lower Yangtze River will continue to experience significant erosion. By the end of 2050, the cumulative total erosion of the mainstream from Yichang to Datong and the three outlets will be 3.58 billion m³ and 117 million m³, respectively. The Dongting Lake is expected to be slightly silted, while the Poyang Lake area will be slightly eroded. Based on these findings, the impacts of the river-lake evolution on flood control, water supply, navigation, ecology, and safety of water-related structures are expounded systematically. Countermeasures and suggestions are also put forward.