- Since radio host Howard Stern continually referred to his wife as "Courteney Cock" in a 2000 interview, Arquette responded by calling the King of All Media "Howard Sperm".
- Jennifer Aniston is the godmother of his daughter, Coco Arquette. She co-starred with his wife, Courteney Cox, on Friends (1994).
- Formerly brother-in-law of actors Nicolas Cage and Thomas Jane who were married to his sister, Patricia Arquette. Former brother-in-law of Tony Greco, James Newton Howard and John Sidel who were married to his sister, Rosanna Arquette.
- Son of Lewis Arquette and Brenda Denaut. Younger brother of Richmond Arquette, Alexis Arquette, Patricia Arquette and Rosanna Arquette. Grandson of Cliff Arquette, better known as "Charley Weaver" from The Hollywood Squares (Daytime) (1965) and Julie Harrison. Uncle of Zoë Bleu Sidel (Rosanna's daughter), Enzo Rossi and Harlow Jane (Patricia's children).
- Entered a rehabilitation program to deal with alcohol abuse and "other issues". [January 2011].
- On a 2002 episode of WWE Monday Night RAW (1993), he sat behind announcers Jerry Lawler and Jim Ross for the entire show while holding a sign reading "Former WCW Champion". He was there simply as a fan, and the announcers never acknowledged him.
- He, Neve Campbell and Courteney Cox are the only three actors to appear in all four "Scream" films. Liev Schreiber appeared in the first three, but not the fourth. Although Jamie Kennedy appeared in the first three films, his character only appeared on a videotape in the third.
- Is a distant relative of explorer Meriwether Lewis.
- Traveled to Africa for the first time as part of "Malaria No More", to witness with his own eyes the devastation Malaria has had on several regions of Senegal. (August 2011)
- He is in a rock band called EAR2000.
- The family surname was spelled "Arcouet" many generations back. His father had French-Canadian, English, Swiss-German, German, Scottish, Irish, and Welsh ancestry. David's maternal grandfather, Yusseff "Joseph" Nowack, was a Jewish immigrant from Bila Zerkwa, Kiev, then in the Russian Empire, while David's maternal grandmother, Claire Hibel, was born in New York, to Russian Jewish parents.
- David Arquette is a certified Bob Ross painter. He has trained in the painting style of Bob Ross and can formally teach Bob Ross' style of oil painting to new artists.
- On WCW Thunder (1998) on 4/27/00, he became the WCW Heavyweight Champion in a special tag match, pitting him and his partner Diamond Dallas Page against Jeff Jarrett and Eric Bischoff. The stipulation was that whoever got the pin would become champ, and after his involvement in previous matches, Arquette was able to pin Bischoff and win the title.
- During a live televised event in Los Angeles, the WWF was "fighting" an invasion from WCW and ECW. Arqutte, Billy Corgan of The Smashing Pumpkins and Arnold Schwarzenegger were all in attendance at the event in one night. This is interesting for that fact that David was a former WCW talent, Billy was a loyal ECW supporter and Arnold had always been a WWF supporter. The WWF showed each one of them on screen. David got a huge laugh for wearing a mask and then ripping it off to show who he was.
- Was considered for the role of Detective Shane Vendrell on The Shield (2002).
- His wedding to Courteney Cox was held at San Francisco's Grace Cathedral.
- He is the 1-800-CALL-ATT Guy.
- Owns the former booking chair from the West Hollywood Police Department which was sat in by a number of different stars when they were arrested, among them Hugh Grant. David has mentioned this to Hugh, and publicly offered to give the chair to him on Late Night with Conan O'Brien (1993) in October of 2003.
- He was among two people to be a non wrestler and hold the WCW World Title, the other was Vince Russo, a booker. Another non wrestler who held another title was Eric Bischoff, as WCW Hardcore Champion. The company was sold within a year of all of this.
- Is the voice of Eddie Wachowski, a character in the EA Sports Big game SSX Tricky (2001) (for Playstation2, Nintendo Gamecube, Xbox).
- Was succeeded in the role of Augustus McCrae in the "Lonesome Dove" film series by Steve Zahn. He and Zahn have both appeared on episodes of Friends (1994).
- He played a character whose last name is "Geller" in Never Been Kissed (1999). His wife Courteney Cox plays "Monica Geller" on Friends (1994). He appeared in Buffy the Vampire Slayer (1992), the title role of which was later portrayed in the TV show of the same name by Sarah Michelle Gellar, who appeared in Scream 2 (1997) with Arquette.
- Longtime friend of Stacy Keibler.
- In 1990, he managed to appear in two unsuccessful television series based on popular movies: Parenthood (1989) (in which he played the role originally played by Keanu Reeves), and The Outsiders (1983) (in which he played the role originally played by Emilio Estevez).
- 13 June 2004: birth of his daughter, named Coco Riley Arquette Coco Arquette. David and Christina McLarty Arquette became the parents of their first child, a boy named Charlie West Arquette, born on April 28, 2014 in Los Angeles, weighing in at 8 lbs. 7 oz. Their second child a boy named Augustus Alexis Arquette, born on March 8, 2017.
- Attended The Los Angeles Center for Enriched Studies in Los Angeles, California.
- Brother-in-law of Todd Morgan, Rosanna's 4th husband.
- He and Robert Duvall, who preceded him in the role of Augustus McCrae, have also both shared a role with a member of the Sheen family. Duvall played Robert E. Lee in Gods and Generals (2003), a role previously played by Martin Sheen in Gettysburg (1993). Arquette played Two-Bit Matthews in the television series The Outsiders (1983), a role previously played by Emilio Estevez.
- Attended Mid-City Alternative school on the corner of Adams Blvd. and Arlington Avenue in the mid 1970s. His sister, Patricia Arquette, and brother, Richmond Arquette, also attended this school.
- Purchased Bozo the clown rights in 2021 from Larry Harmon Pictures Corp., based on his passion for keeping the character's legacy alive and bringing back the silliness and joy of clowns to today's audiences.
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