She made her film debut in Field of Dreams (1989) and found success as a child actress in Uncle Buck (1989), This Is My Life (1992), Sleepless in Seattle (1993), and then later as a teenager with Now and Then (1995), Everyone Says I Love You (1996), Volcano (1997), All I Wanna Do (1998), and 200 Cigarettes (1999).

[9] Herrera was raised in Wiggins, Mississippi by his maternal grandparents; his own father, Gaby's paternal grandfather, was of French and Spanish descent.

[9] Viva and Herrera were estranged shortly after Hoffmann's birth; she was raised by her mother at the Chelsea Hotel in New York.

An entry dated January 10, 1982, two days after Hoffmann was born, says a friend telephoned Warhol and told him they were going to the Chelsea Hotel to see Viva and her new baby.

According to Hoffmann, she and her best friend Talya Shomron roller-skated in the hallways, spied on the drug dealer across the hall, and persuaded the bellman to go to the neighborhood delicatessen at night to fetch them ice cream.

The idea for the 1994 sitcom Someone Like Me originated after Gail Berman (former president of Viacom's Paramount Pictures) read a New York Times article[1] about the hotel which referred to a children's book that Viva and friend Jane Lancellotti wrote, Gaby at the Chelsea (a take on Kay Thompson's 1950s classic Eloise books).

After leaving the Chelsea when Hoffmann was 12,[12] she and her mother moved to the west coast to a two-bedroom rented house in Woodland Hills, Los Angeles, California, which was badly damaged in the January 17, 1994 Northridge earthquake.

[citation needed] After she graduated from Calabasas High School in 1999, Hoffmann followed her half-sister Alex's example and entered New York's Bard College to pursue a degree in literature and writing.

In the same year as Freaky Friday, Hoffmann starred as Young Samantha, the childhood counterpart to Demi Moore's character, in the coming-of-age feature film Now and Then.

Between 1996 and 2001, Hoffmann landed roles in several films including Everyone Says I Love You (1996), Volcano (1997), Snapped (1998), The Hairy Bird (1998), 200 Cigarettes (1999), Coming Soon (1999), Black & White (1999), You Can Count on Me (2000), and Perfume (2001).

She also appeared in the Broadway play SubUrbia, alongside Kieran Culkin and Jessica Capshaw at the Second Stage Theatre on 43rd Street in New York City, which ran from September to October 2006.

[23] Several years later, Hoffmann starred alongside Michael Cera in the adventure comedy film Crystal Fairy & the Magical Cactus (2013) directed by Sebastián Silva.

While shooting the film in Chile, she and Cera took mescaline for her performance,[24] which was nominated for the Independent Spirit Award for Best Female Lead.

[29][13] Her performance was well-received[30] and earned her a nomination for the Primetime Emmy Award for Outstanding Guest Actress in a Comedy Series in 2015.

[31] Joey Soloway, who had watched Hoffman in the third season of Louie, would subsequently write the role Hoffmann plays in Transparent.

[32] In 2016, she appeared in pre-recorded video as an onstage "stand-in" during Sia's Nostalgic for the Present concert tour, for the song "Unstoppable.