Larrea tridentata is a dominant and widespread shrub of North American warm deserts. The species comprises three “chromosomal races,” including diploids (Chihuahuan Desert), tetraploids (Sonoran Desert), hexaploids (Mojave and western Sonoran Deserts), as well as the geographically restricted tetraploid L. tridentata var. arenaria. Creosote bush is a recent arrival to the North American continent, and it is hypothesized that its geographic dispersion reflects rapid ecological divergence mediated by polyploidization. Here we use species distribution modeling to quantitatively evaluate alternate hypotheses for cytotype distributions, based on comprehensive field sampling of creosote bush populations over four years. Using ecological niche models and analyses of field-collected soils, we test whether (1) the climatic niche of the three cytotypes are differentiated; (2) there is evidence for strong climatic gradients at the distributional boundaries of the cytotypes; and (3) cytotype ranges are distinguished by edaphic features. Quantitative tests of niche equivalence indicated that distribution models for all cytotypes were significantly different from one other, suggesting that cytotype races occupy unique and distinctive habitats. However, tests of niche similarity suggest a pattern of niche conservatism, wherein cytotypes tend to occur in climatically similar regions of their respective deserts. Moreover, the modeled diploid distribution was projected to intrude into the geographic range of tetraploids, and the modeled tetraploid distribution was projected to intrude into the range of hexaploids, suggesting that intercytotype competition is a factor influencing cytotype distributions. The range boundary between the dune endemic L. tridentata var. arenaria and hexaploid L. tridentata was noteworthy for exhibiting a strong climatic gradient and striking differences in soil texture (increased sand, decreased gravel). More generally, soil texture differed statistically between sites occupied by diploid, tetraploid, and hexaploid L. tridentata, albeit with considerable overlap across the geographic ranges of the three cytotypes. Taken together, our findings suggest that multiple factors affect the distribution of creosote bush chromosome races, including but not limited to ecological divergence.