Anhedönia officially started making music in 2017, experimenting with "dreamy bedroom pop demos" under different monikers. As White Silas, she first published Gregorian chant-inspired singles and mixtapes to SoundCloud and Tumblr. In 2019, Anhedönia started recording music as Ethel Cain, which became her current main project. For the new moniker, she thought of a "womanly, matronly, old American name", while also taking inspiration from the biblical figure of Cain. Her first extended play as Ethel Cain, Carpet Bed, consisted of four songs and was released on September 13, 2019. Months later, she released her second EP, Golden Age, on December 1. After the latter's release, she was backed by the artist Wicca Phase Springs Eternal, who praised her for her "mature songwriting and understanding of melody". In January 2020, after recommendation from Wicca Phase Springs Eternal, Anhedönia was discovered by the rapper Lil Aaron while headlining a show with Edith Underground, Girlfiend, and Lil Bo Weep in Los Angeles. She was then invited by him to meet with the publishing company Prescription Songs and signed with them soon after.
In February 2021, Anhedönia released her debut single as Ethel Cain while under the new publishing contract, "Michelle Pfeiffer", which featured Lil Aaron. The song was described by Billboard as alternative rock, folk, pop and "even country". Her second single, "Crush", followed on March 18 and received a music video on August 3. The two singles were part of her third EP, Inbred, which was released on April 23. The ambient-folk and slowcore EP was named by Pitchfork as one of The 49 Most Anticipated Albums of Spring 2021 and received a score of 7.6 out of 10 by the website. Later on August 24, a stripped version of "Crush" was also published. On March 8, 2022, she released a cover of the song "Everytime" by Britney Spears as part of Spotify Singles, in observance of International Women's Day.
On March 17, 2022, Anhedönia released the single "Gibson Girl" and subsequently announced her debut album, titled Preacher's Daughter and released on May 12, 2022, through her own record label, Daughters of Cain. A concept album that creates a narrative "centered around the character Ethel Cain", it received a positive reception from music critics and was named one of the best albums of the year. It was also preceded by the release of the singles "Strangers" on April 7 and "American Teenager" on April 21, the latter receiving a music video on July 21. In support of the album, Anhedönia embarked on the Freezer Bride Tour in 2022 and the Blood Stained Blonde Tour in 2023. She was also an opening act at one concert of Florence and the Machine's Dance Fever Tour and Caroline Polachek's Spiraling Tour.
On January 8, 2025, Anhedönia released the studio recording Perverts. An experimental drone project, it was preceded by the release of the lead single, "Punish". In April 2025, Preacher's Daughter received a vinyl release, which caused it to debut on various charts worldwide, including the US Billboard 200 at number ten, marking her first entry on the chart. The album also debuted atop Billboard's Top Album Sales chart.
Anhedönia's second studio album, Willoughby Tucker, I'll Always Love You, was released on August 8, 2025. The album was preceded by the singles "Nettles", and "Fuck Me Eyes". The album serves as a prequel to Preacher's Daughter and accompanied by the Willoughby Tucker Forever Tour.