A signature bridge is an important part of the nation’s infrastructure because of the function it serves, but also because its attests to a country’s economic strength and technological advancement. Panama, is building a major cable-stayed bridge with a design life of in excess of one hundreds of years, therefore it would be beneficial to monitor it so that any departure from assumptions made during design are detected early. During its service life, circumstances and conditions may change, resulting in different types and magnitudes of live load, material variations, natural disasters, and human factors. To ensure safety, the operational functionality and durability of the bridge, it is important to have a comprehensive understanding of the reliability of its structural components. Therefore, a Structural Health Monitoring (SHM) system was needed. This paper outlines the design and implementation of the SHM plan for what will be the world’s largest cable-stayed bridge with a concrete superstructure – The Third Bridge over the Panama Canal at the Atlantic Side. The proposed bridge, which has a 530 m main span, is located in Colon, Panama, one of the most corrosive environments in the world. The paper summarizes the overall objectives, the design principles, recommended types and locations of sensors. The SHM system proposed and implemented included the following aspects: sensor arrays, a data acquisition and transmission system, data processing and control, a health diagnosis methodology, early warning alarms, and a security assessment process. An important focus of the system was related specifically to durability and the monitoring of corrosion in reinforced concrete. Data collected will support and help optimize decision-making on future maintenance and repair. Tension force monitoring in cable-anchorage system was proposed as well to detect changes that might occur due to corrosion or fatigue.