There is an ongoing debate around the extent that anthropogenic processes influence both plant species distribution dynamics and plant biodiversity patterns. Past human food use may leave a strong legacy on not only the extent that food plants are dispersed and fill their potential geographic ranges, but also on food plant species richness in areas that have been densely populated by humans through time. The persistent legacy of plant domestication on contemporary species composition has been suggested to be significant in some regions. However, little is known about the effects that past human food use has had on the biogeography of the Sonoran Desert despite its rich cultural diversity and species richness. I used a combination of ecoinformatics, ethnobotanical, and archaeological data sources to quantitatively assess the impacts of pre-Columbian, and in some cases, more recent, human-mediated dispersal of food plants on the Sonoran Desert landscape. I found that (i) food plants do fill more of their potential geographic ranges than their un-used congeners, and that polyploidy, growth form, and life form are correlated with range filling and past food usage. I also found that (ii) both pre-Columbian and contemporary human population presence are correlated with relative food plant species richness. Thus, both past human food use and contemporary human activities may have influenced the geographic distribution of food plants at regional scales as well as species richness patterns. My research emphasizes that there is an interplay between ecological and anthropogenic processes, and that, therefore, humans must be considered as part of the landscape and included in ecological models.