The actress, who turns 78 next month, will play the grandmother of one of the pupils in The Children's Hour, opening at the Comedy theatre in January.
The American actress Carole Kane will also joined Knightley and Mad Men star Elisabeth Moss in the West End production.
The Children's Hour is set in a girls' boarding school in New England, Lillian Hellman's 1934 play was last performed on the London stage in 1994.
Knightley and Moss - who also makes her West End debut - play a pair of teachers accused of having a lesbian relationship.
Tobias Menzies, famous for playing Brutus in the TV series Rome, has will also join the cast of Ian Rickson's revival.
Born Edna Rae Gillolly in 1932, Burstyn is best known for her roles in horror classic The Exorcist and 2000's Requiem for a Dream. Ellen Burstyn Burstyn won an Oscar for her performance in Martin Scorsese's 1974 film Alice Doesn't Live Here Anymore.