<p>Ecological conservatism is a concept used to characterize a plant species’ fidelity to high-quality natural areas and sensitivity to human impacts. Ecological conservatism is estimated using coefficients of conservatism (C-values), expert-assigned integers that reflect a species’ sensitivity to human impacts. Hotspots of biodiversity—regionally distinct concentrations of biodiversity—have been described in previous studies, and there may be analogous clusters of plant species with greater conservatism resulting from natural biogeographical patterns and human disturbance history. Information on regional variation in plant conservation would highlight floristically unique regions of high conservation value and complement traditional measures of biodiversity. We calculated the mean C-value of county floras (county-C) by using county-level species occurrence data across six Midwestern U.S. states. Our objectives were to: (1) map county-C, (2) determine whether county-C was related to county species richness, and (3) assess how variables reflecting geography and land use history were associated with county-C. Across all six states, counties with the highest county-C were geographically clustered, suggesting hotspots of ecologically sensitive species. Besides Missouri, the highest values were found in the northern parts of the states. Species richness was positively associated with county-C in all states. Across all states, we found an inverse relationship between species’ C-values and the number of counties they occurred in, suggesting that conservatism is associated with limited distributions. Latitude was the strongest predictor of county-C. Natural and agricultural land cover were also strongly associated with county-C; natural cover was positively associated whereas agricultural cover was negatively associated with county-C. Conservative species tend to be geographically concentrated, which could be due to a combination of natural and anthropogenic factors.</p>