The couple met on the set of the movie Scream in 1996 and wed in 1999, having a daughter, Coco, in 2004 before agreeing to separate in 2010 and finalising their divorce three years later.
However, Cox has admitted their dream Hollywood romance was hit by David's decision to ditch leading man roles for a stint in World Championship Wrestling - a passion he has kept up to this day.
"I was on Friends, everything looked pretty good with our careers, then all of a sudden he wants to start wrestling, and I remember feeling embarrassed because there was nothing small about the way he embraced wrestling," she tells The Guardian in a new profile of her ex.
Explaining his love of wrestling, which is documented in a new movie, "You Cannot Kill David Arquette", the star says he inherited his love of sports entertainment from his late dad.
"My dad used to take me to matches, and he was the voice of Superfly Jimmy Snuka (on Hulk Hogan's cartoon, Rock'n'Wrestling)," he reveals. "He died when I was 29 and I really miss him..."
Arquette has since remarried to Entertainment Tonight correspondent Christina McLarty and Cox is in a relationship with Snow Patrol rocker Johnny McDaid - but they will reunite on screen in "Scream 5" next year (21).
Asked if it will be painful seeing his ex-wife, Arquette adds, "No, it's been 10 years now, so there's been a lot of healing."