La Bête, by David Hirson, is set in 17th-century France and was first performed on Broadway in 1991 and later transferred to the West End.
Lumley and Rylance will share the stage with David Hyde Pierce (famed for his role as Dr Niles Crane from American sitcom Frasier).
The production will run at the Comedy Theatre from 7th July until 28th August 2010, before transferring directly to the Shubert Theater on Broadway.
The original production won an Olivier for Best New Comedy and starred Alan Cumming.
Lumley was last on the London stage in 1995 at the Lyric Hammersmith. The Absolutely Fabulous actress performed in The Cherry Orchard at the Sheffield Crucible in 2006.
Hyde Pierce will make his West End debut. He has previously won a Tony Award for Best Performance by a Leading Actor in a Musical for Curtains.
Rylance is currently starring in the West End as Johnny Byron in Jez Butterworth's Jerusalem. The monumental role is a huge winner with audiences and has won him Best Actor at the Evening Standard and Critics Circle Awards.