At 16, Barnett started making music in youth clubs. At 17, she moved to South London to pursue a career as a dancer, where she also attended the BRIT School. After changing her focus from dance to music, she transferred from the BRIT School to Croydon College to pursue an education in fine arts. She worked as a backup dancer in music videos by artists such as Kylie Minogue, Plan B, Ed Sheeran, Taio Cruz, Dionne Bromfield, Jessie J, and Wretch 32. She was a backup dancer for Jessie J in her 2010 video for “Do It like a Dude”, and appeared again in her 2011 video for “Price Tag”. She also appeared in Dionne Bromfield’s video “Yeah Right”. In 2011, she appeared in a two-minute BBC comedy sketch titled Beyoncé Wants Groceries, in which she was a backup dancer in a supermarket. At 18, she began working with local London producers to try to find what she calls “her sound”. Around this time is when she wrote “I’m Your Doll”. She ended up producing a lot of “really bad demos”. For a time, she worked as a hostess in a gentleman’s club and also sang periodically at The Box.

In August 2012, Twigs was photographed for the cover of i-D magazine. She became known as Twigs for the way her joints crack. She added the initialism FKA to her name when a duo called The Twigs, consisting of two twin sisters complained about her use of the name. Several sources have claimed that the “FKA” stands for “Formerly Known As”, but Twigs has said in multiple interviews that the letters do not stand for anything in particular: “[I]t’s just a collection of letters. I was gonna be like FK1 Twigs…or AFK Twigs…I just wanted a selection of letters that sounded quite kind of masculine and strong. FKA just worked. It doesn’t stand for anything, it’s just capital letters.”

Twigs self-released her music debut, EP1 (also called “twigs”), on Bandcamp on 4 December 2012. She posted a video for each song on her YouTube channel. In August 2013, Twigs released the video for her first single, “Water Me”, on YouTube. The video was directed by Jesse Kanda. That same month The Guardian profiled Twigs for their “New Band of the Day” feature, describing her as “the UK’s best example to date of ethereal, twisted R&B.” Twigs’s second extended play, EP2, was released through the Young Turks record label in September. It was produced by Twigs and Arca. Pitchfork gave EP2 a rating of 8/10. In December, she was nominated for the BBC’s Sound of 2014 prize, and she was chosen by Spotify for their Spotlight on 2014 list. Twigs was then featured on Billboard’s 14 Artists to Watch in 2014.

In April 2014, Twigs appeared on the cover of The Fader for its 91st issue. She then directed and starred in the music video for “Ouch Ouch” by rapper Lucki Eck$. She also produced the track. She began writing for her debut studio album during a period of “self-hatred”, which she considers “quite normal” for a young person. Twigs’s debut studio album, LP1, was released in August through Young Turks. Time magazine gave the album a positive review, saying that Twigs has “made that transition to one of the most compelling and complex acts in R&B.” Twigs then announced a world tour starting on 2 October at The Dome in Brighton, East Sussex and ending on 3 December in Orlando, Florida at The Social.

In August 2014, Twigs was signed to London-based production company Academy Films as part of their A+ roster. She has since uploaded three videos on 20 August to her YouTube Channel which she directed: a video titled “Wet Wipez”, starring the London dance crew of the same name, a video titled “tw-ache”, which is a remix of the EP1 song “Ache”, and a video for the Lucki Eck$ track “Ouch Ouch”, which she also produced.

In September 2014, LP1 was revealed as one of the nominees for the 2014 Mercury Prize. The same month, Twigs performed on BBC’s Later… with Jools Holland. In October, a video for “Video Girl” was released, as well as an advert for Google Glass which Twigs directed. Twigs made her US television debut on The Tonight Show Starring Jimmy Fallon on 4 November.

On 7 November 2014, producer Boots announced he was working with Twigs on her third EP. The video for “Glass & Patron”, the first song released from the EP, was posted Twigs’s official YouTube channel on 23 March 2015. It was directed by Twigs. In February 2015, she performed Congregata, a theatrical “coming together” and choreographed performance that visualised “the story of my life while making this album” at the Roundhouse in Camden London.

In September 2014, Twigs began dating actor Robert Pattinson. They were rumoured to be engaged, but never publicly confirmed it. The couple split in the summer of 2017.

On 15 May 2015, on her official Instagram account, she posted a picture of men posing with jackets on that had an image of Twigs’ face from the “Papi Pacify” video with Twigs captioning the pic “coming soon… <3”, hinting at either FKA Twigs merchandise or EP3’s alleged release in the summer. During an interview with Complex magazine released in June, she stated that she had changed the title of the EP to Melissa, and that it would be released within two months. She confirmed it would include the songs “Glass & Patron”, “Mothercreep”, “I’m Your Doll”, “Figure 8”, and “In Time”. The EP, stylised as M3LL155X, was released on 13 August 2015, containing all five tracks and accompanied by four videos, which were directed by Twigs herself, featuring pregnancy, sex dolls, vogueing and Rick Owens’ wife Michele Lamy. The title of the EP reads as “Melissa” and is named after the artist’s “personal female energy”.

On 18 February 2016, Twigs debuted a new song and music video titled “Good to Love”. The song premiered at Soundtrack 7, her seven-day residency at Manchester International Festival that took place in July 2015. She also performed the song on The Tonight Show Starring Jimmy Fallon on 24 February 2016. On 9 July 2016, Twigs debuted a new stage show called “Radiant Me²” at Moscow’s Lastochka Festival, where she unveiled three previously unheard songs.

In August 2016, the dance film Soundtrack 7 was premiered. Directed by Twigs, the film was created, performed and filmed on-site across seven days at Manchester International Festival in 2015.

Twigs appeared on A$AP Rocky’s album Testing in 2018, featuring on the track “Fukk Sleep”.

In May 2018, Twigs revealed via Instagram that she underwent surgery to remove fibroid tumors from her uterus in December 2017. She described her experience as “living with a fruit bowl of pain every day” and saluted the bravery of other women living with the condition.

On 24 April 2019, Twigs released her single, “Cellophane”, her first release since “Good to Love” in 2016. In September 2019, Twigs announced her second album, co-produced with Nicolas Jaar, would be titled Magdalene, supported by second single “Holy Terrain” (featuring Future) on 9 September. On 7 October 2019, Twigs released a third single, “Home with You”, and announced that the album would be delayed until 8 November. She also acted in the 2019 film Honey Boy.

In August 2020, she appeared in an OnlyFans-inspired music video for the song “Sum Bout U” with rapper 645AR.