Streamflow and sediment loads undergo remarkable changes in worldwide rivers in response to climatic changes and human interferences. Understanding their variability and the causes is of vital importance regarding river management. With respect to the Changjiang River (CJR), one of the largest river systems on earth, we provide a comprehensive overview of its hydrological regime changes by analyzing long time series of river discharges and sediment loads data at multiple gauge stations in the basin downstream of Three Gorges Dam (TGD). We find profound river discharge reduction during flood peaks and in the wet-to-dry transition period, and slightly increased discharges in the dry season. Sediment loads have reduced progressively since 1980s owing to sediment yield reduction and dams in the upper basin, with notably accelerated reduction since the start of TGD operation in 2003. Channel degradation occurs in downstream river, leading to considerable river stage drop. Lowered river stages have caused a 'draining effect' on lakes by fostering lake outflows following TGD impoundments. The altered river-lake interplay hastens low water occurrence inside the lakes which can worsen the drought given shrinking lake sizes in long-term. Moreover, lake sedimentation has decreased since 2002 with less sediment trapped in and more sediment flushed out of the lakes. These hydrological changes have broad impacts on river flood and drought occurrences, water security, fluvial ecosystem, and delta safety.