Arquette was born in New York City, the daughter of Brenda Olivia "Mardi" (née Nowak; 1939–1997), an Actress, poet, theater operator, Activist, acting Teacher, and therapist, and Lewis Arquette, a film actor, Screenwriter, and Producer. Her paternal grandfather was Comedian Cliff Arquette. Her mother was Jewish, from a family that emigrated from Poland and Russia. Her father, whose family's surname was originally "Arcouet", was of part French Canadian descent. Her father was a convert from Catholicism to Islam; through him, Arquette is distantly related to Explorer Meriwether Lewis. Her siblings, Patricia, Alexis, Richmond, and David, are also actors.