The channel stability and change trend of Xuliujing node reach are of pivotal importance in the evolution of the Yangtze River Estuary as it controls the material flux and the diversion and sediment distribution of the north and south branches of the Yangtze River Estuary. The stability of the channel in Xuliujing node reach and its influencing factors were studied via measured data analysis and physical model test. Results demonstrated that: 1) before 1992, the river channel in Xuliujing reach shifted to the right; from 1992 to 2018, the evolution of the river channel attenuated, displaying a small upward and downward trend on horizontal scale, and a slow downward trend on vertical scale. 2) In future, the pattern of shoal and trough in Xuliujing node reach would remain stable in general; the channel would be dominated by scour and develop towards the downstream; big floods will see conspicuous adjustments of local beds—a new -30 m trough will appear 910 meters downstream of the existing -30 m channel under the condition of 2009-2018 plus one-in-100-year hydrological years. 3) In early stage, the overall stability of Xuliujing reach is mainly affected by enclosure project, upstream and downstream river regime, and flood, while in recent years, it is mainly affected by sediment reduction of the river basin. Flood and human activities are major influencing factors of local riverbed stability.