Water transportation accidents have occurred frequently in recent years. In order to improve the emergency response capability of water transportation systems under traffic-intensive conditions, this paper identifies and analyzes the vulnerability in traffic-intensive areas of water transportation systems. Firstly, the vulnerability identification model was constructed based on the analysis of characteristics and the vulnerability-influencing factors of water transportation systems. The newly proposed model is composed of three parts including the DEMATEL (Decision Making Trial and Evaluation Laboratory) method, ISM (interpretative structural modeling) model, and AHP (Analytic Hierarchy Process)–entropy weight method. Finally, a case study of the Yangtze River was conducted to test the logicality and feasibility of the proposed model. The research results reveal that traffic flow density, ship traffic, tides, fog, and bad weather are the key factors affecting the vulnerability of water transportation in traffic-intensive areas of the Yangtze River estuary. However, the influence of navigation aid configuration, berth, anchorage, and obstruction on the system vulnerability is relatively lower. The findings of this study can provide helpful references for maritime administration authorities on the management of water transportation safety.