Knightley was nominated for a best actress Oscar in 2006
Keira Knightley will make her West End debut opposite fellow British actors Damian Lewis and Tara Fitzgerald in Moliere's The Misanthrope in December.
The 24-year-old star of films including Atonement and Pirates of the Caribbean, will play American film star Jennifer.
Lewis, best known for US series Band of Brothers, will play the title role - a disillusioned playwright who falls for the ambitious and mercurial Jennifer.
The play opens at the Comedy Theatre on 17 December and runs until 13 March.
The production, adapted by playwright Martin Crimp, moves the action from 17th century Paris to modern-day London.
It will be directed by Thea Sharrock, whose previous credits include directing Daniel Radcliffe and Richard Griffiths in the West End production of Equus, and later on Broadway.
Knightley recently completed work on two films, London Boulevard and Never Let Me Go, both due for release next year.
Lewis finished filming the US TV series Life earlier this year.