Anthropogenic disturbances associated with the rapid development of coastal cities have drastically influenced the hydrodynamics and sediment transport processes in many large estuaries globally. Lingdingyang Estuary (LE), located in the central and southern part of the Pearl River Delta, southern China with a long history of high-intensity anthropogenic disturbances, was studied to explore the contribution rate and mechanism underlying the alteration in hydrodynamics and sediment transport under each phase of human activity. A state-of-the-art modeling tool (TELEMAC-2D), was used to study the variations in the hydrodynamics and sediment transport, accounting for reclamation-induced shoreline and dredging-induced topography changes. The results indicated that: i) under the influence of successive land reclamation, the general distribution of the Confluence Hydrodynamic Zone (CHZ) in LE varied from scattered to concentrated, and these zones moved 3–5 km seaward. ii) Large-scale channel dredging weakened the residual flow in LE, decreasing the residual flow in the Inner-Lingding Estuary (ILE) by 62.45%. This was initiated by the enhancement of tidal dynamics through changes in the bottom friction caused by dredging in the ILE. In contrast, massive reclamation decreased the residual flow in the ILE by 17.55% and increased that in the Outer-Lingding Estuary (OLE). iii) Despite disturbances related to land reclamation and dredging, the estuarine jet flow in LE remained a turbulent jet system, and the estuarine jet flow became more asymmetrical. In addition, the position of the estuarine jet source moved 6–13 km seaward. iv) Both reclamation and dredging decreased the SSC in the ILE and increased the SSC in the OLE. Reclamation weakened the SSC in the ILE by 62.19%, whereas dredging enhanced the SSC in the OLE by 49%. Spatially, reclamation resulted in an increase in the SSC near the outlets and a decrease in the SSC in the northern portion of the Western Channel. Dredging mainly increased the SSC in the northern part of the OLE. v) The increase in the barotropic pressure gradient was the main factor driving the enhancement of the residual flow and SSC near the outlets. Moreover, the southward location of the “artificial outlets” favored the transport of suspended sediments to the OLE, which was one of the primary reasons for the increase in the SSC in the OLE. Finally, the tidal dynamics of the ILE intensified due to massive reclamation and dredging. The findings of this study indicate that hydrodynamics and sediment transport in LE have greatly changed over the last decades, with reclamation and dredging being the crucial drivers. The insights obtained from this study can serve as a reference for the comprehensive management of the Pearl River Estuary and other large estuaries experiencing similar anthropogenic forcing.