The actor, best known for TV dramas Life On Mars and State of Play, is following in the footsteps of David Tennant and Jude Law as the latest actor to play the Danish prince.
The production will premiere at the Sheffield Crucible in September 2010, following a £15.3m redevelopment of the theatre.
Daniel Evans, the venue's artistic director, told the BBC that it was "very exciting" to have Simm on board.
"When a major actor like John comes along, who people know for his brilliant TV work, it is a privilege to make it happen," he said. "[Associate director] Paul [Miller] and John have this brilliant long-standing relationship and he knew immediately who his ideal Hamlet would be. It is potentially a very scary role, but it has become one of those roles that every major actor leaps through. It can be a test of your mettle."
Simm is currently appearing in Speaking In Tongues in London's West End.