Born in Los Angeles, she was the fourth of five children to Lewis Arquette, an actor and director, and Brenda Olivia "Mardi" (née Nowak), an actress.

Coming from a family deeply entrenched in the entertainment industry, Alexis was the sibling of actors Rosanna, Richmond, Patricia, and David Arquette.

Her career began in her youth, appearing aged 12 in the music video "She's a Beauty" by The Tubes and making her screen debut in Down and Out in Beverly Hills (1986).

Known for her versatility, Arquette often performed as a female impersonator under the name "Eva Destruction", before publicly sharing her transition process towards gender-affirming surgery.

[8] In 1986, Arquette made her big screen debut in an uncredited role as Alexis, the androgynous friend and bandmate of sexually ambivalent teenager Max Whiteman (Evan Richards) in Down and Out in Beverly Hills.

[citation needed] That same year, Arquette guest starred in the Friends episode "The One with Chandler's Dad", in which she directly interacted with her sister-in-law, Courteney Cox.

On January 31, 2007, Arquette was a featured celebrity client and guest judge on the première episode of Bravo's reality show Top Design.

She decided against undergoing hormone therapy and kept her choice of whether she underwent gender-affirming surgery private from the media by the time she completed her transition in 2006.