The period drama, created by Waking The Dead's Richard Warlow, will focus on H Division, the notorious police precinct charged with keeping order in Whitechapel, during the aftermath of the 'Jack the Ripper' murders.
BBC head of drama Ben Stephenson confirmed the casting of Macfadyen at the recent Broadcasting Press Guild lunch.
The former Spooks star's recent credits include 2011 blockbuster The Three Musketeers and Channel 4 mini-series Any Human Heart.
Stephenson has also confirmed that Hayley Atwell will star in two-part drama Restless, adapted by Any Human Heart author William Boyd from his own novel.
The Captain America: The First Avenger star will play a young woman who finds out that her mother was a spy during World War II.
Atwell appeared alongside Macfadyen in Any Human Heart and recently filmed a role in the big-screen adaptation of The Sweeney.
Both series will air later in 2012.
> William Boyd, Sally Wainwright to pen BBC dramas