As inherently community-driven processes, the dynamics of vector-borne diseases are closely tied to landscape characteristics that may impact the composition and diversity of animal communities. Habitat fragmentation, in particular, can modulate the composition and diversity of vertebrate communities that serve as important bloodmeal or reproductive hosts for zoonotic vectors such as ticks. However, the relationship between changes in the ecological landscape, host community composition, and tick-borne disease risk is not well resolved. While some studies document greater risk of tick-borne disease in more fragmented landscapes, others show that disease risk is greater in more intact habitats. Fundamental to this discordance may be a lack of consistency in how both fragmentation and host communities are measured and evaluated. We sought to address this issue by evaluating different dimensions of habitat fragmentation and standardizing how host community composition is characterized to better understand the ecological drivers of tick-borne disease risk along a habitat fragmentation gradient. Our approach empirically determined how landscape features such as patch size, Euclidean distance, and host-specific cost distance to source sites affect the risk of the Lyme disease bacterium as well as overall tick-borne disease richness. Using field and molecular data across six years, we examined 19 habitat fragments that ranged in size from 2.5 hectares to over 150,000 hectares and characterized host diversity, abundance, and measured the risk of tick-borne pathogens. We found that habitat patch size and proximity to source habitat were the most important landscape metrics that drove the risk of the density of Lyme disease infected ticks as well as overall tick-borne pathogen richness as well. At the same time, the diversity of rodents and predators both positively influenced the prevalence of infection in ticks, especially the Lyme disease bacterium. Our results demonstrate complexity vector disease dynamics on human-modified landscapes and illustrate the importance of considering landscape ecology to better understand and control vector-borne disease.