Flooding is the most frequent disaster in China. It affects people’s lives and properties, causing considerable economic loss. Flood forecast and operation of reservoirs are important in flood emergency management. Although great progress has been achieved in flood forecast and reservoir operation through using computer, network technology, and geographic information system technology in China, the prediction accuracy of models are not satisfactory due to the unavailability of real-time monitoring data. Also, real-time flood control scenario analysis is not effective in many regions and can seldom provide online decision support function. In this research, a decision support system for real-time flood forecasting in Yujiang River Basin, South China (DSS-YRB) is introduced in this paper. This system is based on hydrological and hydraulic mathematical models. The conceptual framework and detailed components of the proposed DSS-YRB is illustrated, which employs real-time rainfall data conversion, model-driven hydrologic forecasting, model calibration, data assimilation methods, and reservoir operational scenario analysis. Multi-tiered architecture offers great flexibility, portability, reusability, and reliability. The applied case study results show the development and application of a decision support system for real-time flood forecasting and operation is beneficial for flood control.