Identifying links between environmental variables and infectious disease risk is essential to understanding how human-induced environmental changes will effect the dynamics of human and wildlife diseases. Although land cover change has often been tied to spatial variation in disease occurrence, the underlying factors driving the correlations are often unknown, limiting the applicability of these results for disease prevention and control. In this study, we described associations between land cover composition and West Nile virus (WNV) infection prevalence, and investigated three potential processes accounting for observed patterns: (1) variation in vector density; (2) variation in amplification host abundance; and (3) variation in host community composition. Interestingly, we found that WNV infection rates among Culex mosquitoes declined with increasing wetland cover, but wetland area was not significantly associated with either vector density or amplification host abundance. By contrast, wetland area was strongly correlated with host community composition, and model comparisons suggested that this factor accounted, at least partially, for the observed effect of wetland area on WNV infection risk. Our results suggest that preserving large wetland areas, and by extension, intact wetland bird communities, may represent a valuable ecosystem-based approach for controlling WNV outbreaks.