Alexis Arquette was born Robert Arquette in Los Angeles, California, the fourth of five children of Brenda Olivia “Mardi” (née Nowak), an actress, poet, theater operator, activist, acting teacher, and therapist, and Lewis Arquette, an actor and director. Mardi Nowak was Jewish of Russian and Polish descent. Lewis Arquette was a convert to Islam from Catholicism. Lewis’s family’s surname was originally “Arcouet” of partial French-Canadian ancestry; Lewis’s father was comedian Cliff Arquette. Alexis Arquette was distantly related to American explorer Meriwether Lewis. Actors Rosanna, Patricia, Richmond, and David Arquette are her siblings. In 1982, at the age of 12, Arquette’s first acting gig was as “this little kid who’s on a ride with all these women and whatnot” in the music video “She’s a Beauty” by The Tubes. In 1986, Alexis Arquette debuted on the big screen 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.

At nineteen, Alexis Arquette landed her first sizable film role, playing transvestite Georgette in the screen adaptation of Last Exit to Brooklyn. The majority of Arquette’s film work was in low-budget or independent films. In total, she starred in more than 40 movies, including I Think I Do, Children of the Corn V: Fields of Terror, and Sometimes They Come Back… Again. She also starred as a crack addict opposite Tim Roth in Jumpin’ at the Boneyard, as a man seeking revenge for a horrible childhood in the New Zealand-shot fantasy Jack Be Nimble, and as a murderous drag queen in the low budget comedy Killer Drag Queens on Dope. She also had supporting roles in Threesome and Bride of Chucky,[11] and she played a Boy George impersonator in the Adam Sandler-Drew Barrymore films The Wedding Singer and Blended. In 2001, Arquette returned to New Zealand to play Roman emperor Caligula in two episodes of Xena: Warrior Princess. That same year, Arquette guest starred in the Friends episode “The One with Chandler’s Dad” and cameoed in Son of the Beach. In September 2005, VH1 announced Alexis Arquette as one of the celebrity house-guests on the 6th season of The Surreal Life. On January 31, 2007, Arquette was a featured celebrity client and guest judge on the première episode of Bravo’s reality show Top Design. Arquette also made a cameo appearance in Robbie Williams’ “She’s Madonna” video.

In her late 30s, Alexis Arquette transitioned from male to female. Her experiences were documented in the film Alexis Arquette: She’s My Brother, which debuted at the 2007 Tribeca Film Festival. Arquette was a vocal supporter of transgender people, including Chaz Bono, who also transitioned from 2006 to 2008. Alexis Arquette died on September 11, 2016, reportedly from AIDS-related complications. Arquette’s brother Richmond posted on Facebook, “Our brother Robert, who became our brother Alexis, who became our sister Alexis, who became our brother Alexis, passed this morning September 11, at 12:32 am. He was surrounded by all of his brothers and sisters, one of his nieces and several other loved ones. We were playing music for him and he passed during David Bowie’s ‘Starman’. As per his wishes, we cheered at the moment that he transitioned to another dimension.”