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Abstract Background The West Nile virus is a highly contagious agent for a wide range of hosts. Its spread in the Mediterranean region raises several questions about its origin and the risk factors underlying the virus’s dispersal. Materials and methods The present study aims to reconstruct the temporal and spatial phylodynamics of West Nile virus lineage 2 in the Mediterranean region using 75 complete genome sequences from different host species retrieved from international databases. Results This data set suggests that current strains of WNV-2 began spreading in South Africa or nearby regions in the early twentieth century, and it migrated northwards via at least one route crossing the Mediterranean to reach Hungary in the early 2000s, before spreading throughout Europe. Another introduction event, according to the data set collected and analyses performed, is inferred to have occurred in around 1978. Migratory birds constitute, among others, additional risk factors that enhance the geographical transmission of the infection. Conclusion Our data underline the importance of the spatial–temporal tracking of migratory birds and phylodynamic reconstruction in setting up an efficient surveillance system for emerging and reemerging zoonoses in the Mediterranean region.