Ecologists have studied geographic gradients in biodiversity for decades and recently mapped the intensity of the “human footprint” around the planet. The combination of these efforts have identified some global hotspots of biodiversity that are heavily impacted by human-caused land cover change and infrastructure. However, other hotspots of biodiversity experience less intense modifications from humans. Relationships between species diversity and the human footprint may be driven by covarying factors, like climate, soils, or topography, that coincidentally influence patterns of biodiversity and human land use. Here, I investigated relationships between tree species richness and the degree of human modification among Forest Service ranger districts within the contiguous US. Ranger districts with more tree species tended to experience greater human modification. Using data on climate, soils, and topography, I explored mechanisms explaining the positive relationship between tree richness and human modification. I found that climate is related to both tree richness and human modification, which may be indirectly mediated through climate’s role governing productivity. Ranger districts with more productive climates support more species and greater human modification. To explore potential conservation consequences of these relationships, I also investigated whether the amount of area designated within highly protected conservation lands were related to climate, productivity, and topography. Less productive ranger districts with steeper slopes tended to experience the greatest relative amounts of conservation protection. Combined, these results suggest that complex relationships explain the geographic patterns of biodiversity and the human footprint, but that climate and topography partially govern patterns of each.