[7] Sweeney was raised in north Idaho[8] in the state's Panhandle region along the Washington border, at a rural lakeside home that her family has inhabited for five generations.

Sweeney said she had a wakeboarding accident as a child where the edge of her board propelled backward and sliced the area next to her eye, leaving a permanent scar.

[12] Sweeney began to audition and book commercial acting jobs in Seattle and Portland, Oregon, where the family temporarily resided, until choosing to relocate to Los Angeles when she was 13 years old.

[16] Sweeney began her career as a guest star in TV shows such as 90210, Criminal Minds, Grey's Anatomy and Pretty Little Liars.

[17][18] Sweeney starred as Emaline Addario on the 2018 Netflix series Everything Sucks!, which revolved around two groups of high school students in Oregon in 1996.

She then appeared in the HBO miniseries Sharp Objects, recurring as Alice, a roommate whom Amy Adams' character meets at a psychiatric facility.

[23] She had a recurring role during the second season of the dystopian drama series The Handmaid's Tale as Eden Spencer, a pious and obedient girl from the totalitarian and theocratic Republic of Gilead.

[25][26][27] In June 2019, Sweeney began portraying Cassie Howard, a teenager with a promiscuous reputation, in the HBO drama series Euphoria.

[29] Her performance received praise, earning a nomination for the Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series in 2022.

[30] Variety asserted that the role of Cassie "proves that Sweeney's one hell of a shapeshifter between her deft turns in this, The Handmaid's Tale, Everything Sucks and Sharp Objects.

[33] The same year, she starred in the TV film Nocturne as well as Webtoon’s live-action advertisement for the online comic Lore Olympus, appearing as Persephone.

[39] For her portrayal of the character, she was nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Limited or Anthology Series or Movie in 2022.

"[43] Jessica Kiang of Variety wrote that she played "Winner so convincingly that it's hard to remember her as the sardonic, pampered teen in The White Lotus, or the nice-girl-turned-nasty in Euphoria.

[52] Sweeney was an executive producer for the film and was instrumental in hiring costar Glen Powell and director Will Gluck in addition to contributing to the script.

[65] She will also produce and star in an as-yet untitled biopic of boxer Christy Martin[66] and will reprise her role of Cassie Howard in the third season of Euphoria.