Although Jesus had been introduced as a character in previous episodes, this marked the first time he interacted with the main characters outside of his public access talk show, Jesus and Pals. Trey Parker said many viewers thought the character was a crazy person who falsely believed he was Jesus, and he and Stone wanted to show in this episode that he was supposed to be the actual Jesus.
Michael Buffer, the boxing ring announcer best known for his catchphrase, "Let's get ready to rumble!", made a guest appearance as himself. Trey Parker and Matt Stone originally planned to use the catchphrase without Buffer, but when they learned that Buffer had legally trademarked the phrase, they included him in the episode since getting the rights for the catchphrase cost nearly as much as hiring Buffer for a guest appearance. Parker and Stone both said Buffer was friendly and they enjoyed working with him.
In the "Damien" episode, the words chanted by the choir of voices are "Rectus, Dominus, Cheesy Poofs". "Rectus Dominus" is mock Latin for "Ass Master", an insult commonly used on Cartman. "Cheesy Poofs" is the brand name of Cartman's favorite snack in the series.
Mike Judge had originally been slated to provide the voice of the Damien character, and even recorded several lines for the part. However, since Judge lives in Austin, Texas, it proved too difficult to for him to come back and rerecord lines as the script and episode changed, so Matt Stone instead provided the character's voice.
Cartman receives Ants in the Pants, an actual children's tabletop game, as a birthday present. Matt Stone described Ants in the Pants as "the lamest game ever", which is why Cartman responds so negatively to the gift in the episode.