Significance Louse-borne relapsing fever was one of the major diseases affecting Western human populations, with its last major pandemic killing millions after World War I. Despite the major role fevers have played in epidemic events throughout history, molecular evidence for the presence of their etiological agent has been extremely scarce in historical samples worldwide. By comparing our medieval Borrelia recurrentis genome with modern representatives of the species, we offer an historical snapshot of genomic changes in an immune-evasion system and of reductive evolution in a specialized vector-borne human pathogen. This shotgun sequencing project highlights the potential for ancient DNA research to uncover pathogens which are undetectable to osteological analysis but are known to have played major roles in European health historically.