The actor will play the lead in Henrik Ibsen's An Enemy of the People at Chichester Festival Theatre in April.
The play is part of artistic director Jonathan Church's final season at the West Sussex venue.
Bonneville's last full stage play was 2004's Cloaca, directed by Kevin Spacey at London's Old Vic.
He last appeared at Chichester in The Handyman (1996).
In Christopher Hampton's version of Ibsen's 1882 drama, Bonneville plays Dr Stockmann - whose discovery of contamination at the popular local baths splits opinion about whether the truth should come out.
Directed by Howard Davies, An Enemy of the People runs from 22 April to 21 May.
The new Chichester season, announced on Thursday, includes "two musicals, two new plays and four epic dramas".
Joseph Fiennes will play Lawrence of Arabia in Terence Rattigan's 1960 drama Ross, directed by Adrian Noble, at the Festival theatre in June.
The season begins in April with Patricia Hodge and Steven Pacey leading the cast in the world premiere of new musical Travels with my Aunt, based on Graham Greene's novel, featuring songs by George Stiles and Anthony Drewe.
The same songwriters have added songs to a new stage version of Half a Sixpence, opening in July, with a book  by Downton Abbey writer Julian Fellowes and original songs by David Heneker.
The two new plays in the Minerva Theatre are black comedy Fracked! Or: Please Don't Use the F-Word by Alistair Beaton, featuring James Bolam and Anne Reid; and Mark Hayhurst's First Light, about the impact of World War One on soldiers and their families.
The Olivier Award-winning actor Bertie Carvel makes his directorial debut with a revival of John Galsworthy's Strife, a rarely staged play about a workers' strike at a Welsh tin factory.
Carvel, who recently starred at the Old Vic in Eugene O'Neill's The Hairy Ape, said: "It's a joy and a privilege to be given the opportunity to stage this great play at what couldn't be a more apposite moment.
"I've been lucky to spend the last 10 years working with some of the best directors around. I'll be luckier still if some of it has rubbed off on me."
Downton Abbey star Hugh Bonneville is returning to the stage for his first full theatre run in more than a decade.