The Nile River is the lifeblood of Egypt. The necessity to rationalize Nile's water uses and protecting from pollution and accidents in Egypt is an urgent issue. Continuous monitoring and utilizing the early warning system (EWS) were becoming important tools to protect and manage water sources for sustainable development. The aim of this study is to design and propose guidelines for the establishment of an (EWS) in real-time to ensure the safety of Nile water in Egypt and to mitigate the water pollution disaster by terrorism and accidents. To achieve this objective, (1) it is reviewed the EWS basic structure regarding risk knowledge, monitoring system, active communication of information and the plans for readiness and response (case study the Rhin river), (2) it is assessed the current water quality monitoring in the Nile and the current problems regarding the implementation of the early warning system for Nile water quality, (3) it is examined the characteristics of a Nile EWS, and (4) it is recommended a roadmap for establishing the proposed EWS. The roadmap for EWS describes a process in four steps, a start-up by a letter of interest from all ministers, organizational setup, implementation and testing, and continuous improvement. A steering committee consisting of the main ministries recruited from the National Council for the protection of the Nile that determines responsibilities, and that can take corrective actions to optimize the EWS. The proposed EWS will provide a sufficient information database for the decision-makers in sustainable water management.