Arquette was born in Chicago, Illinois, the daughter of Lewis Arquette, an actor, and Brenda "Mardi" Olivia (née Nowak), an actress, poet, theater operator, activist, acting teacher and therapist. Arquette's mother was Jewish, the daughter of a Holocaust refugee from Poland, and Arquette's father was a convert to Islam and related to explorer Meriwether Lewis. Her paternal grandfather was comedian Cliff Arquette, and her siblings are actors Rosanna, Alexis, Richmond and David Arquette.
In 1987, Arquette's first starring roles were as pregnant teenager Stacy in television film Daddy, boarding school student Zero in Pretty Smart, and the attention-getting Kristen Parter in A Nightmare on Elm Street 3: Dream Warriors. In 1991, she won a CableACE Award for her portrayal of a deaf epileptic in Wildflower. In 1993, she starred in Tony Scott's True Romance. She has since appeared in such critically acclaimed movies as Ed Wood as the "worst ever" film director's eventual wife, Beyond Rangoon, Ethan Frome, Lost Highway, Little Nicky, Stigmata, Bringing Out the Dead, Human Nature, Disney's Holes, and Flirting with Disaster.
In 1987, Arquette's first starring roles were as pregnant teenager Stacy in television film Daddy, boarding school student Zero in Pretty Smart, and the attention-getting Kristen Parter in A Nightmare on Elm Street 3: Dream Warriors. In 1991, she won a CableACE Award for her portrayal of a deaf epileptic in Wildflower. In 1993, she starred in Tony Scott's True Romance. She has since appeared in such critically acclaimed movies as Ed Wood as the "worst ever" film director's eventual wife, Beyond Rangoon, Ethan Frome, Lost Highway, Little Nicky, Stigmata, Bringing Out the Dead, Human Nature, Disney's Holes, and Flirting with Disaster.