In the episode, Ned Flanders is shocked after seeing a new display at the museum about evolution. Together with Reverend Lovejoy, he spreads the religious belief of creationism in Springfield, and at a later town meeting, teaching evolution is made illegal. As a result, Lisa decides to hold secret classes for people interested in evolution. However, she is quickly arrested and a trial against her is initiated.

J. Stewart Burns wrote "The Monkey Suit", for which he received inspiration from the 1925 Scopes Monkey Trial. The episode features a few references to this legal case, as well as several references to popular culture. Many analysts have commented on the episode's treatment of the creation–evolution controversy, a dispute about the origin of humanity between those who support a creationist view based upon their religious beliefs, versus those who accept evolution, as supported by scientific evidence.