Efficient communication and coordination are needed between countries to prevent, detect and respond to international food safety events. While communication tools, networks and systems exist, current evidence suggests that they are only useful within particular contexts and several only target specific geographic areas. There is a need to unpack and explore the mechanisms of how and in what context such communication tools and their components are effective at facilitating international communication and coordination to keep food safe and mitigate the burden of foodborne disease around the world. A realist synthesis was undertaken to understand how and why certain processes and structures of communication tools, used during international food safety events, influence their utility and effectiveness according to different contextual factors. The focus of this review was explanatory and aimed to develop and refine theory regarding how contextual factors trigger specific processes and mechanisms to produce outcomes. Using the realist context–mechanism–outcome configuration of theory development, a range of sources was used to develop an initial programme theory, including the authors’ experience, a scoping review of published papers and grey literature and input from an expert reference committee. Literature was then systematically located and synthesised from several databases with input from the expert reference committee to refine the programme theory. The programme theory developed indicates that when a country has interests in food import or export, has the technical infrastructure to detect and respond to food safety events, and is governed in accordance with regional and/or global laws and regulations relating to food control and global health security, then specific mechanisms will facilitate various outcomes. Mechanisms include trust, experience, support, awareness, understanding, a sense of community, standardisation and intersectoral collaboration. The outcomes include using communication tools to relay information abroad and the prevention of foodborne diseases, among others. Components of such communication tools may be adapted according to different contextual factors to promote, support and improve their use. Improving international coordination and communication during international food safety events is in the interest of global health security and can mitigate the global burden of foodborne disease.