AbstractSalmonella Enteritidis is a major foodborne pathogen that causes both local and international outbreaks with complex transmission pathways. Invasive infections which are associated with multidrug resistance are an increasing concern around the globe. However, the global epidemiological picture of S. Enteritidis remains unclear due to the lack of a fine scale typing scheme based on genomic sequencing data. Here, using the novel multilevel genome typing (MGT) approach, we have characterised the genomic epidemiology of S. Enteritidis in unpreceded detail. We examined 26,670 publicly available S. Enteritidis whole genome sequences from 86 countries over 101 years to reveal their spatial and temporal distributions. Using MGT4 and MGT5, we identified globally prevalent and regionally restricted STs. Source associated STs were identified, such as poultry associated MGT4-STs, which were common in human cases in the USA. Temporal trends were observed in the UK with MGT5-STs from 2014 to 2018, revealing both long lived endemic STs and the rapid expansion of new STs. Using MGT3 to MGT6, we identified MDR associated STs to facilitate tracking MDR spread. The majority of the global S. Enteritidis population fell within two predominant lineages with significant differences in geographic distribution, outbreak frequency, antimicrobial resistance and mutation rate. An online open MGT database has been established for unified international surveillance of S. Enteritidis. We demonstrated that MGT provides a flexible and high-resolution genome typing tool for S. Enteritidis surveillance and outbreak detection.