Eve Best will return to Shakespeare's Globe this summer to star in Antony and Cleopatra, which runs from 17 May to 24 August 2014.
Best made her directing debut at the Globe last year with Macbeth, and previously appeared as Beatrice in the 2011 production of Much Ado About Nothing. Other recent credits include the Old Vic's production of The Duchess of Malfi and playing Wallis Simpson in the Oscar-winning film The King's Speech.
She won the Olivier Award for Best Actress for her performance in the title role in Hedda Gabler at the Almeida in 2005.
Antony and Cleopatra will be directed by Jonathan Munby and also features Phil Daniels (The God of Soho) in the role of Enobarbus.
Further casting is still to be announced.
Other Shakespeare productions in this year's 'Arms and the Man' season, themed around war and the classical world, are Lucy Bailey's Titus Andronicus, Dominic Dromgoole's Julius Caesar and Blanche McIntyre's The Comedy of Errors.
Directed by Lindsay Posner, the cast features the previously announced Sinéad Cusack and Clare Higgins.
Plimpton, who will mark her London stage debut, is also a respected stage actress whose Tony-nominated Broadway credits include Top Girls, Coast of Utopia and Pal Joey.
In Other Desert Cities she plays Brooke Wyeth, who returns to the family home in Palm Springs for the first time in six years with some incendiary news for her Republican parents Polly and Lyman, her brother Trip and her recovering alcoholic aunt Silda. She is about to publish a memoir about her family, exposing a pivotal moment in their painful and explosive past, her actions threatening to push fractured family relations to a point beyond repair.
Other Desert Cities is the first in a new season of productions which will be presented in-the-round at The Old Vic, echoing the venue's 2008 season.