Fragmentation of the landscape has been proposed to play an important role in defining local scale heterogeneity in Lyme disease risk through influence on mammalian host density and species composition. We tested this observed relationship in a suburban region around Lyme, Connecticut, where we collected data on the density of the tick vector, Ixodes scapularis and prevalence of the Lyme bacterium, Borrelia burgdorferi at 30 sites. Analysis of the landscape pattern of forest patches was performed using satellite imagery. The calculated landscape indices, which included patch size and isolation, revealed a positive link between fragmentation and both tick density and infection prevalence in ticks. In spite of higher entomologic risk, human incidence of Lyme disease is lower in fragmented contexts suggesting that entomologic risk is not the critical driver of human infections. These results represent a departure from the prior claims that fragmentation and human Lyme disease risk are positively linked. A complete understanding of the influence of landscape fragmentation will allow for improved risk mapping and potential environmental management of Lyme disease.