Japanese barberry (Berberis thunbergii de Candolle) is a thorny, perennial, exotic, invasive shrub that is well established throughout much of the eastern United States. It can form dense thickets that limit native herbaceous and woody regeneration, alter soil structure and function, and harbor increased blacklegged tick (Ixodes scapularis Say) populations. This study examined a potential causal mechanism for the link between Japanese barberry and blacklegged ticks to determine if eliminating Japanese barberry could reduce tick abundance and associated prevalence of Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt, and Brenner). Japanese barberry was controlled at five study areas throughout Connecticut; adult ticks were sampled over three years. Each area had three habitat plots: areas where barberry was controlled, areas where barberry remained intact, and areas where barberry was minimal or absent. Sampled ticks were retained and tested for B. burgdorferi presence. At two study areas, temperature and relative humidity data loggers were deployed in each of the three habitat plots over two growing seasons. Intact barberry stands had 280 ± 51 B. burgdorferi-infected adult ticks/ha, which was significantly higher than for controlled (121 ± 17/ha) and no barberry (30 ± 10/ha) areas. Microclimatic conditions where Japanese barberry was controlled were similar to areas without barberry. Japanese barberry infestations are favorable habitat for ticks, as they provide a buffered microclimate that limits desiccation-induced tick mortality. Control of Japanese barberry reduced the number of ticks infected with B. burgdorferi by nearly 60% by reverting microclimatic conditions to those more typical of native northeastern forests.