These genetically-mutated creatures were made accidentally by Rick in the episode Rick Potion No. 9 when he tried to turn the "Mantis-people" back into regular Humans. Everyone on Earth became Cronenbergs except for Jerry, Beth, and Summer, due to being closely related to Morty. In another universe, where everyone had previously been Cronenbergs (Cronenberg World), the opposite happened and everyone were accidentally turned into savage Humans by Cronenberg Rick and Morty. They both fled to dimension C-137 to continue living among Cronenbergs.
In The Rickshank Rickdemption, it has been shown that Jerry, Beth, and Summer have been subsisting on Cronenberg meat for some time. This indicates that, up until that point, at least a small population of Cronenbergs survived since the date of their mutation.
In Rick and Morty Issue 45, Cronenberg Morty explains to Summer (C-137) that the Cronenbergs of dimension C-137 are just savage creatures, whereas the Cronenbergs of Cronenberg World were civilized and more like humans.
- The word/name Cronenberg is a reference to Canadian filmmaker, screenwriter, actor, and director David Cronenberg. This is due to the fact that Cronenberg is one of the originators of the "body horror" genre in which the style of filmmaking explores people's fears of bodily transformation and infection.
- Near the ending of "Auto Erotic Assimilation", the frozen alien that Rick destroyed with the lazer is shown to be a Cronenberg. This suggests that Rick was still trying to cure Cronenberg mutation and also suggests that he gave up on the idea.