Best known for his role in the "Scream" movies, Arquette has also appeared in the films "Beautiful Girls," "The Alarmist" and "Ravenous."
His casting in "Earl" was confirmed Wednesday by show creator and executive producer Greg Garcia.
"In the episode, scheduled to air this fall, Earl (Jason Lee) decides it's time to make it up to local stunt man, Sweet Johnny (Arquette,) for sleeping with his girlfriend 10 years ago," NBC said in a release. "When Earl finds Sweet Johnny, he discovers his friend has a permanent injury that makes righting the wrong seem almost impossible. Elsewhere, Joy (Jaime Pressly) buys a gun after someone carjacks the Brat, but Darnell (Eddie Steeples) does not approve of owning the firearm."
The fourth season premiere of "My Name is Earl" is to air Sept. 25.