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The second plague pandemic, caused by  Yersinia pestis , devastated Europe and the nearby regions between the 14 th  and 18 th  centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient  Y. pestis  genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a  Y. pestis  lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541–750 AD), suggesting a comparable evolutionary trajectory of  Y. pestis  during both events.

Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes