The Glaswegian will be appearing at the Music Hall in the Assembly Rooms as part of the 75th anniversary season of the Fringe in August.
He will join fellow Scots comics Fern Brady and Susie McCabe in Assembly’s confirmed programme for this summer.
Boyle’s last major run of Fringe shows was in a 1200-capacity room at the EICC, while the Music Hall has a capacity of around 670.
Boyle made his name performing at The Stand Comedy Club in Edinburgh in the mid-1990s and won an open-mic award at the Fringe in 1996.
He rose to prominence thanks to appearances on TV shows like Mock The Week, Have I Got News For You and Would I Lie to You.
Despite pledging to retire from stand-up before he turned 40, Boyle has regularly toured.
Now 49, he has been confirmed for a headline appearance at the Fringe by the Sea festival in North Berwick in August.
An announcement on his Fringe show, entitled Lap of Shame, says: “As part of a continuing physical and mental tailspin, Frankie Boyle suppresses his overarching sense of futility and horror to tell jokes for an hour in the final days of organised human life.
“It’s a show largely about politics, satirising whichever new leaders emerge from the irradiated rubble. The show will then embark on a tour of Re-education Camps, Robot Barracks, and Colosseums built from old shipping containers.”Rich Hall, Clive Anderson, Nish Kumar, Isabelle Farah, David O’Doherty, Des Bishop, Julia Masli, Michelle Brasier are among the other comedy stars in the Assembly programme.
It will also feature a Kate Bush-inspired drag act, Britain's Got Talent finalist Magical Bones, Western-themed circus spectacular Railed, “ghost whispering” cabaret act Séayoncé Space Hippo, a Japanese shadow puppet show from Japan, and a tribute to the music and songs of Victoria Wood by cabaret star Paulus.
Fringe favourites returning to the Assembly fold this year include the hit satirical singing trio Fascinating Aida and late-night party show Massaoke.
William Burdett-Coutts, Assembly’s artistic director, said: “This incredible line-up of shows illustrates the enormous enthusiasm there is from artists to return to Edinburgh this August.
“After two very difficult years for our industry, it is wonderful to see how much the festival has been missed by so many local and international performers who have been longing to return with their new work and Fringe favourite five-star shows.
“We really hope audiences will come back to the festival in their droves and have a fantastic time, so that the Fringe can once again be seen the world-over as the leading cultural celebration of live performance.”
Other new Fringe shows announced this week include the return of cabaret favourites La Clique and The Tiger Lillies, part of Underbelly’s programme, which also includes magician Tom Brace, hip hop sensation Abandoman and comic Jason Byrne.
Gilded Balloon’s line-up includes magicians Pete Firman and Kevin Quantum, comics Maisie Adams, Lost Voice Guy, Elf Lyons, Esther Manito and Jamie MacDonald, and the return of Basil Brush.
Pleasance highlights include a revival for Trainspotting Live, an “immersive adaptation of Irvine Welsh’s debut novel, and Porno, a new stage version based on the sequel.