Based on the flow, sand, and topographic data during the flood seasons of 2005 and 2014, the three-dimensional (3D) numerical model of flow and sediment and the mechanism decomposition of suspended sediment flux were utilized to analyze the changing rules of the hydrodynamics and sediment dynamics in the Jiaojiang River Estuary under the influence of human activities. In addition, the process of sediment transport in the estuary was discussed, as well as the change in the mechanism and its influencing factors. The results show that dominated by the overall topographic change of the river, the tidal dynamics and sediment dynamics in the estuary change significantly; by taking Shixianfu as the demarcation, the upstream flood tide advantage is enhanced, and the downstream flood tide advantage is weakened, but the current velocity of the flood tide and the ebb tide along the river is increased. The distribution of the estuarine turbidity maximum moves upstream for more than 36 km, and the average sediment concentration in the section between Miaolonggang and Shixianfu increases by about 5 kg/m³, while that in the section between Shixianfu and Haimen increases by about 3 kg/m³. The increase in the sediment concentration and tidal asymmetry in the upper reaches of the river leads to a stronger tidal pumping effect on sediment transport in the estuary and varying total amounts and directions of sediment transport during the spring and neap tides. This in turn causes a mechanism shift from the “estuarine sediment transport to the sea at the upstream and to the land at the downstream” in terms of spatial characteristic difference to the “sediment transport to the land during spring tide and to the sea during neap tide” in terms of the tidal type distribution difference, which thus affects the characteristics of riverbed erosion and deposition.