Lyme borreliosis (LB) is the archetypal emerging zoonosis and is dependent on transmission by ticks in the genus Ixodes. Understanding the origin, maintenance, and spread of these ticks contributes much to our understanding of the spread of LB and other disease agents borne by these ticks. We collected 1232 Ixodes scapularis ticks from 17 east coast sites ranging from New Hampshire to Florida and used mtDNA, three nuclear genetic loci, and incorporated Bayesian analyses to resolve geographically distinct tick populations and compare their demographic histories. A sparse, stable, and genetically diverse population of ticks in the Southeastern US, that is rarely infected with the agent of LB is genetically distinct from an abundant, expanding, and comparatively uniform population in the Northeast, where epidemic LB now constitutes the most important vector borne disease in the United States. The contrasting geography and demography of tick populations, interpreted in the context of the geological history of the region, suggests that during the last glacial period such ticks occupied distinct refugia, with only the northern-most site of refuge giving rise to those ticks and pathogens now fueling the epidemic.