She self-released her first two albums, Lush (2012), and Retired from Sad, New Career in Business (2013), while studying studio composition at Purchase College's Conservatory of Music.

Mitski signed with Dead Oceans in 2015 and released Puberty 2 (2016), Be the Cowboy (2018), and Laurel Hell (2022), the last of which made the top ten in several countries.

[4] That same year, she co-composed "This Is a Life" with Son Lux for the film Everything Everywhere All at Once, which earned her an Academy Award nomination for Best Original Song.

During her time at Purchase, she recorded and self-released her piano-based first and second albums, Lush (2012) and Retired from Sad, New Career in Business (2013), as student projects.

In 2013, she collaborated with indie-rock artists Mike Rasimas and Mutsawashe Mangwendeza, providing vocals for the original song Ego and a cover of "Nightcall" by Kavinsky.

[32] Her song "Francis Forever" was covered by Olivia Olson as the character Marceline the Vampire Queen in a 2016 episode of the Cartoon Network show Adventure Time.

The compilation aims to raise funds for organizations that support causes threatened by Donald Trump's proposed policies.

[40] On May 14, 2018, Mitski opened pre-orders for her fifth studio album, Be the Cowboy, and released the lead single, "Geyser", with an accompanying music video.

[43] The song’s chorus, where she repeatedly sings "Nobody", became widely used in TikTok trends, often paired with surreal memes or individuals running away from the camera.

[44] This virality introduced Mitski’s music to a broader audience, leading to a significant streaming boost—Be the Cowboy re-entered Billboard’s Top 200 in 2021, three years after its release.

"[12] Mitski worked with performance artist Monica Mirabile to devise the tour's "highly stylized, sometimes unsettling" movements.

I'm going to keep getting hurt, and I'm still going to do it, because this is the only thing I can do.’"[57]Mitski shared her new song, "Cop Car", in January 2020,[58] a never-released piece from the soundtrack of The Turning.

The sci-fi Western story written by Chris Miskiewicz and Vincent Kings "unpacks themes of theology, death, and the afterlife".

These experiences involved a pre-release listening party for The Land Is Inhospitable and So Are We alongside a screening of a film chosen personally by Mitski: these films included Terrence Malick’s Days of Heaven, Donna Deitch’s Desert Hearts, Gus Van Sant’s Drugstore Cowboy and Federico Fellini’s La Strada.

[74] Mitski also announced six concert dates set to take place in the United Kingdom, Germany, the Netherlands, and France.

Mitski described these dates as "not a full-blown tour", but intimate and small enough to preview the album without elaborate stage production.

[76] In November 2023, it was announced that Mitski was attached to write lyrics and music for a Broadway adaptation of the 1983 novel The Queen's Gambit.

Accompanied by Patrick Hyland on acoustic guitar and Jeni Magaña on double bass, she covered “Coyote, My Little Brother” and “Buffalo Replaced.”[78][79] E. Alex Jung described her as "an artist whose music feels like being ushered into a private opera house of melodrama" with lyrics full of "roiling fury, destructive impulses, humiliation, longing, heartache, and hunger".

[13] Angie Martoccio of Rolling Stone described her earlier albums as a "wry running commentary on twentysomething angst, raw desire, and often unrequited love".

Lucy Dacus, a singer-songwriter who has at times opened for Mitski, described her music as "really visceral… She's connected to a part in herself that wants to scream.

[82] In 2021, former President of the United States Barack Obama included "The Only Heartbreaker" in his yearly list of top songs.

She has stated her main reason for quitting was that she had a difficult time grappling with newfound indie stardom when her 2018 album Be the Cowboy hit the mainstream.

[82] Her fanbase has been described as "extremely online", "cultish",[4] and as rivaling "Taylor Swift and BTS in intensity, if not size".

Recalling an instance where she had to proceed through an audience unescorted to her dressing room, she said: "Everyone needed a piece of me […] I was so overwhelmed by hands grabbing at me that I was crying.