Exotic plants often invade areas of high human activity, such as along trails, roads, and forest edges, and in disturbed riparian areas. These same habitat types are also favored by ticks. This convergence suggests that habitat modifications caused by exotic plant invasions may mediate disease vector habitat quality, indirectly affecting human disease risk at the local spatial scale. We tested the hypothesis that experimental invasions of Japanese stiltgrass, Microstegium vimineum (Trin.) A. Camus, alter soil surface microclimate conditions, thereby reducing habitat quality for ticks. Microstegium is an exotic annual grass that is highly invasive throughout the eastern United States where the vector ticks Amblyomma americanum (Linnaeus) and Dermancentor variabilis (Say) occur. Ticks (n = 100 per species) were introduced into experimentally invaded and native vegetation control plots (n = 5 per treatment). D. variabilis mortality rate increased 173% and A. americanum mortality rate increased 70% in the invaded plots relative to those in control plots. Microstegium invasion also resulted in a 13.8% increase in temperature and an 18.8% decrease in humidity, which are known to increase tick mortality. We predict that areas invaded by Microstegium will have lower densities of host-seeking ticks and therefore reduced human disease risk. Our results emphasize the role of invasive species in mediating disease vector populations, the unpredictable consequences of biological invasions, and the need for integrative management strategies that can simultaneous address exotic plant invasions and vector-borne disease.