This study investigates the phylogeographic patterns and key drivers of West Nile virus (WNV) spread in Europe. Using viral genome sequences and epidemiological data, the researchers mapped the evolution and spread history of WNV in Europe. Spatially explicit phylogeographic models were developed to explore the possible contribution of different drivers to viral dispersal direction and velocity. A "skygrid-GLM" approach was used to identify how changes in environments would predict viral genetic diversity variations over time. Among the six lineages found in Europe, WNV-2a (a sub-lineage of WNV-2) has been predominant, accounting for 73% of all sequences obtained in Europe. WNV-2a has spread to at least 14 countries and has evolved into two major co-circulating clusters, both originating from Central Europe, but with distinct dynamic history and transmission patterns. WNV-2a spreads at a high dispersal velocity (88 km/yr–215 km/yr), which is correlated to bird movements. Factors related to land use were found to strongly influence the spread of WNV. Specifically, the intensity of agricultural activities (defined by factors related to crops and livestock production, such as coverage of cropland, pasture, cultivated and managed vegetation, livestock density) were positively associated with both spread direction and velocity. In addition, WNV spread direction was associated with high coverage of wetlands and migratory bird flyways. The study suggests that in addition to ecological conditions favoring bird- and mosquito-presence, agricultural land use may be a significant driver of WNV emergence and spread. The study also identified significant gaps in data and the need to strengthen virological surveillance in countries of Central Europe from where WNV outbreaks are likely seeded. Enhanced monitoring for early detection of further dispersal could be targeted to areas with high agricultural activities and habitats of migratory birds. The study highlights the importance of understanding the drivers of WNV spread to improve preparedness for potential outbreaks.This study investigates the phylogeographic patterns and key drivers of West Nile virus (WNV) spread in Europe. Using viral genome sequences and epidemiological data, the researchers mapped the evolution and spread history of WNV in Europe. Spatially explicit phylogeographic models were developed to explore the possible contribution of different drivers to viral dispersal direction and velocity. A "skygrid-GLM" approach was used to identify how changes in environments would predict viral genetic diversity variations over time. Among the six lineages found in Europe, WNV-2a (a sub-lineage of WNV-2) has been predominant, accounting for 73% of all sequences obtained in Europe. WNV-2a has spread to at least 14 countries and has evolved into two major co-circulating clusters, both originating from Central Europe, but with distinct dynamic history and transmission patterns. WNV-2a spreads at a high dispersal velocity (88 km/yr–215 km/yr), which is correlated to bird movements. Factors related to land use were found to strongly influence the spread of WNV. Specifically, the intensity of agricultural activities (defined by factors related to crops and livestock production, such as coverage of cropland, pasture, cultivated and managed vegetation, livestock density) were positively associated with both spread direction and velocity. In addition, WNV spread direction was associated with high coverage of wetlands and migratory bird flyways. The study suggests that in addition to ecological conditions favoring bird- and mosquito-presence, agricultural land use may be a significant driver of WNV emergence and spread. The study also identified significant gaps in data and the need to strengthen virological surveillance in countries of Central Europe from where WNV outbreaks are likely seeded. Enhanced monitoring for early detection of further dispersal could be targeted to areas with high agricultural activities and habitats of migratory birds. The study highlights the importance of understanding the drivers of WNV spread to improve preparedness for potential outbreaks.