When making the second season, Cartoon Network wanted David Feiss to keep on making "I. M. Weasel" shorts. David Feiss didn't want to make any more, but agreed he would only if he could start using the Red Guy in the "I. M. Weasel" shorts. Since then, the Red Guy was a regular character in Weasel.
The episode "Buffalo Gals" was banned after its first airing, due to sexual references and lesbian stereotypes. The episode involved a pack of biker girls who wore buffalo hats (hence the name) busting into Cow and Chicken's house and tearing up the place. The leader takes a liking to Cow and they kidnap her, which means Chicken must go to her rescue.
The first Cow and Chicken short had rougher animation than the series that followed, and featured much darker themes. In the first cartoon, Chicken goes to Hell for smoking cigarettes, and is tortured by The Devil while he's there. After this harsh episode, the content of the series was toned down, the animation was brightened up, and The Devil's name was changed to "The Red Guy".
It was David Feiss' ex-wife Pilar Menendez's idea to have Cow's alter-ego, Supercow speak only in Spanish.
A banned episode depicts lesbians. This was the first time to show a same gender relationship in a kids show. It was never looked at again until an episode of the show Clarence (2013), when it was depicted that Jeff had two moms. Strangely, only two weeks after that episode premiered, The Last Stand (2014) became the first show to have a main character fall in love with someone of the same gender in a kids show, as the characters Korra and Asmi begin a relationship.