According to the Daily Mail, Macfayden will reunite with his Pride & Prejudice director on the project, which tells the story of a bored wife, played by Keira Knightley, who embarks on an affair with a young lover.
Macfadyen will star as Knightley's brother Oblonsky, while Boardwalk Empire star Kelly Macdonald has also signed on to play his character's wife Dolly.
Hanna stars Olivia Williams and Saoirse Ronan have also joined the project, along with Brighton Rock actress Andrea Riseborough.
It has previously been confirmed that Jude Law will portray Knightley's aristocrat husband, while Kick-Ass star Aaron Johnston will play her lover.
Anna Karenina begins filming this September in both London and September.
Watch Joe Wright discussing Anna Karenina below: