She has also appeared in The Mosquito Coast (1986), Shy People (1987), Running on Empty (1988), Parenthood (1989), Samantha (1991), Small Town Murder Songs (2011), Frozen II (2019), and Mass (2021).

Other theatre productions in which she has performed include The Playboy of the Western World, A Midsummer Night's Dream, The Glass Menagerie, The Sisters Rosensweig, and Uncle Vanya.

[3][4][5] She played Virginia Chance in the Fox sitcom Raising Hope, which earned her a Primetime Emmy Award nomination for Outstanding Lead Actress in a Comedy Series.

[15] Plimpton began her career as a model, securing an early 1980s campaign for Calvin Klein, making an impression as a sophisticated but tomboyish little girl.

[17] In 1984, she appeared in the Deep South drama The River Rat opposite Tommy Lee Jones, as his "hoydenish daughter".

This began Plimpton being cast in the role of a rebellious tomboy,[16] beginning with her performance as the Reverend Spellgood (Andre Gregory)'s daughter in the 1986 film The Mosquito Coast, starring Harrison Ford.

[16] The critically praised but commercially unsuccessful 1987 film Shy People [21] was followed by a performance in the 1988 ensemble comedy Stars and Bars.

[20][22] This was released shortly before Running on Empty, an Oscar-nominated film,[23] in which Plimpton appeared opposite River Phoenix, her boyfriend, both 17–18 years of age, like their characters.

Plimpton appeared in the Robert De Niro-Jane Fonda 1990 romantic drama Stanley & Iris in a supporting role.

[54] From August to September 2007, Plimpton appeared in A Midsummer Night's Dream in the Public Theater Shakespeare in the Park production as "Helena".

Plimpton received her second nomination for a Tony Award in 2008, Best Performance by a Featured Actress In a Play, for her work in Top Girls at the Biltmore Theater.

[56] In November 2008, she earned a positive review from Ben Brantley in The New York Times for her role as Gladys Bumps in the Roundabout Theatre Company production of Pal Joey on Broadway: "...the ever-daring Ms. Plimpton exudes a been-there, frowzy sensuality that summons a host of hard-bitten dames from 1930s movie melodramas.

[60] In 2010, she sang another Springsteen song, "Thunder Road", on the public radio program Studio 360 with Kurt Andersen, accompanied by whistler Eric Gilliland.

[62] Plimpton is on the board of directors of The Players,[63] a New York City social club founded in 1888 by actor Edwin Booth.

"[65] Plimpton was nominated for the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series for her portrayal of Virginia Chance in Raising Hope.

Her performance, well received by critics, included songs "Jolly Coppers on Parade", "Woman Is the Nigger of the World", and The Smiths's "Ask" tied together with humorous monologues.

[67] Plimpton also narrates audiobooks, including the novels Diary by Chuck Palahniuk[68] and Mrs. Kimble by Jennifer Haigh.

[69] She had a recurring role in the CBS legal drama The Good Wife from 2009 to 2013, playing attorney Patti Nyholm, who appeared through four seasons.

[70] Plimpton sang "God Bless America" during the seventh inning stretch of Game 3 of the 2010 World Series in Texas on Fox, October 30, 2010.

[71] On December 15, 2010, Chicago's Steppenwolf Theatre announced that Plimpton would be the guest of honor at their second-annual "Salute to Women in the Arts".

[72] In 2010, she starred in Ed Gass-Donnelly's independent crime thriller Small Town Murder Songs, and was given a trophy for best actress by the Whistler Film Festival.

[73] In 2014, Plimpton returned to Broadway as Julia, the daughter of Glenn Close and John Lithgow in a revival of Edward Albee's A Delicate Balance.

[87] In 2014, Plimpton wrote a lengthy article decrying both U.S. Supreme Court decisions in Burwell v. Hobby Lobby and McCullen v. Coakley and revealing in part that she herself has had an abortion more than once.