Over the past century, fire suppression has facilitated broad ecological changes in composition, structure, and function of fire-dependent landscapes of throughout the eastern US which are in decline. These changes have likely contributed mechanistically to the enhancement of habitat conditions that favor pathogen carrying tick species, key wildlife hosts of ticks, and interactions that have fostered pathogen transmission among them and to humans. While the long-running paradigm for limiting human exposure to tick-borne diseases focuses responsibility on individual prevention, the continued expansion of medically important tick populations, increased incidence of tick-borne disease in humans, and emergence of novel tick-borne diseases highlights the need for additional approaches to stem this public health challenge. Another approach that has the potential to be a cost effective and widely applied, but remains largely overlooked, is the use of prescribed fire to ecologically restore degraded landscapes that favor ticks and pathogen transmission. We examine the ecological role of fire and its effects on ticks within the eastern US, especially examining the life cycles of forest-dwelling ticks, shifts in regional-scale fire use over the past century, and the concept that frequent fire may have helped moderate tick populations and pathogen transmission prior to the “fire suppression era” that has characterized the past century. We explore mechanisms of how fire and ecological restoration can reduce ticks, the potential for incorporating the mechanisms into the broader strategy for managing ticks, and the challenges, limitations, and research needs of prescribed burning for tick reduction.