The behavioral immune system (BIS) is an evolved psychological mechanism that motivates prophylactic avoidance of disease vectors by eliciting disgust. When felt toward social groups, disgust can dampen empathy and promote dehumanization. Therefore, we investigated whether the BIS facilitates the dehumanization of groups associated with disease by inspiring disgust toward them. An initial content analysis found that Nazi propaganda predominantly dehumanized Jews by portraying them as disease vectors or contaminants. This inspired three correlational studies supporting a Prophylactic Dehumanization Model in which the BIS predicted disgust toward disease-relevant outgroups, and this disgust in turn accounted for the dehumanization of these groups. In a final study, we found this process of prophylactic dehumanization had a downstream effect on increasing anti-immigrant attitudes during the COVID-19 pandemic. However, consistent with the evolutionary logic of a functionally flexible BIS, this effect only occurred when the threat of COVID-19 was salient. The implications of these results for the study of dehumanization and evolutionary theories of xenophobia are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s40806-021-00296-8.