St. Vincent produced Sleater-Kinney's ninth studio album The Center Won't Hold (2019) and co-wrote Taylor Swift's Billboard Hot 100 number-one single "Cruel Summer".

[16] In 2004, she joined Glenn Branca's 100-guitar orchestra for the Queens performance,[24] and she was also briefly in a noise rock band called the Skull Fuckers.

In an interview on The Colbert Report, she said that she "took [her] moniker from a line in a Nick Cave song" that referred to the hospital where Dylan Thomas died: "And Dylan Thomas died drunk in / St. Vincent's hospital" (from Cave's song "There She Goes, My Beautiful World", from the 2004 album Abattoir Blues / The Lyre of Orpheus).

"[30] The songs on Marry Me were written largely when Clark was 18 and 19, and, she says, "represented a more idealized version of what life was or what love was or anything in the eyes of someone who hadn't really experienced anything.

Her inspiration reportedly came from several films, including Disney movies: "Well, the truth is that I had come back from a pretty long — you know, about a year-and-a-half of touring, and so my brain was sort of all circuit boards that were a little bit fried", Clark said.

"[33] Clark, who did not have a studio at the time, began writing the album in her apartment on her computer using GarageBand and MIDI, because she had gotten noise complaints from neighbors.

[21] Spin gave the album eight out of ten stars, noting its "[juxtaposition of] the cruel and the kind, and here, the baroque arrangements are even more complex and her voice even prettier, with both only underlining the dark currents running through her songs".

[36] Entertainment Weekly said the album "plays up the contrasts, [with Clark] letting her church-choir voice linger on lyrics that hint darkly at themes of violence, sex, and general chaos", and branded it "a uniquely potent cocktail of sounds and moods".

A promotional music video for "Laughing with a Mouth of Blood", featuring Portlandia's Fred Armisen and Carrie Brownstein (then of ThunderAnt), was also filmed.

In November 2010, Clark appeared with American rappers Kid Cudi and Cage on Late Night with Jimmy Fallon.

They performed "Maniac" from Cudi's Man on the Moon II: The Legend of Mr. Rager, which prominently samples "The Strangers", the opening song on Actor.

In an interview with Julie Klausner for Spin magazine, she recalled: "[Death Cab for Cutie drummer] Jason McGerr had an office that was closing.

[45] On August 25, 2011, she debuted Strange Mercy in the Temple of Dendur room at the Metropolitan Museum of Art in New York City,[46] introducing Toko Yasuda (ex-Enon), Matt Johnson, and Daniel Mintseris as members of her live band.

[citation needed] In 2011, Clark composed "Proven Badlands", an instrumental piece based on "The Sequel" from her sophomore release Actor, for ensemble Music's album Beautiful Mechanical.

[52][53] On September 18, 2012, Clark participated in the "30 Songs / 30 Days" campaign to support Half the Sky: Turning Oppression into Opportunity for Women Worldwide, a multiplatform project inspired by Nicholas Kristof and Sheryl WuDunn's bestselling book.

[56] In November 2013, Clark received the Smithsonian American Ingenuity Award for Performing Arts[57] and signed to Loma Vista Recordings.

[62] On April 10, 2014, Clark fronted Nirvana, performing lead vocals on "Lithium" at the 29th Rock and Roll Hall of Fame induction ceremony.

[65] Clark toured the United States, Europe, Australia, and Asia throughout 2014, ending the year as the supporting act for the Black Keys.

She extended her Digital Witness tour into the summer of 2015,[66] and performed alongside the Pixies and Beck at Boston Calling Music Festival in May 2015.

[67] A demo of "Teenage Talk", a track she had previously recorded but that was not included on her eponymous album,[68] premiered on the HBO series Girls on March 10, 2015.

[87] In late 2020, St. Vincent was featured on the track "Chalk Tablet Towers" from the first season of the Song Machine project by Gorillaz.

Additionally, she wrote the film's soundtrack, releasing on digital streaming services on September 17, 2021, and later on limited vinyl on April 23, 2022, as part of Record Store Day.

[96] On June 3, 2022, St. Vincent released her cover of Lipps Inc.'s "Funkytown" appearing on the soundtrack for Illumination's film Minions: The Rise of Gru.

A profile in The New York Times after the album's release noted: "Seven albums and 17 years into an acclaimed solo career, Clark has eked out a singular space in music, occasionally intersecting with the mainstream but for the most part staying uncompromisingly countercultural," labeling tracks from the new release "some of the heaviest, darkest and weirdest St. Vincent music to date.

[105] Clark’s music, which features her mezzo-soprano voice,[106][107][108] has been noted for its wide array of instruments and complex arrangements, as well as its polysemous lyrics, which have been described as teetering between "happiness and madness".

[120] Talking Heads, Patti Smith and Pink Floyd are also influences,[121] as well as guitarists Robert Fripp and Adrian Belew (both from King Crimson),[122] Marc Ribot and Tool.

[130][131] In 2017, four additional colors were added to the guitar line, Polaris White, Heritage Red, Tobacco Burst, and Stealth Black.

[134] In 2021, a new St. Vincent Goldie signature model was released, featuring three gold foil mini-humbucker pickups, a reverse matching finish headstock, redesigned pickguard shape in 3-ply parchment, a roasted maple neck, and stainless steel frets.

[135][136] Notable users of the guitar include Jack White, who used the three pickup version during every performance of his Boarding House Reach tour in 2018, Todd Tamanend Clark, Tom Morello, J Mascis, Les Priest of LANY, Eva Hendricks of Charly Bliss, Emily Roberts of The Last Dinner Party, and Dan Boeckner of Wolf Parade.

"[145] Later that year, in an interview with the UK's Sunday Times, she elaborated: "I'm not one for gender or sexual absolutism in the main; I fully support and engage in the spectrum.