Williams will take up the role of Alphonse Frankenstein and Rooper will play the Maid of Honour, Justine Moritz.
The pair join Lacey Turner (Being Human, EastEnders) as Elizabeth Lavenza, Andrew Gower (Monroe) as Victor Frankenstein and Robin Hood star David Harewood as the Creature.
Jemima Rooper says: “It’s a very unusual and ambitious project – I’ve just finished a musical so I am really looking forward to being able to sing again.”
Airing on Saturday 19th March, the project will explore Mary Shelley’s gothic masterpiece through live drama and contemporary music for one night only at Leeds’ Kirkstall Abbey.