The comic, whose New World Order returns to BBC Two tonight, will take the role of the tyrannical, blind, chair-bound character Hamm for a run at the Gate Theatre in Dublin in February.
The dark, harrowing comedy follows Hamm and his resentful servant Clov who are locked in a stalemate, whilst Hamm's senile parents are confined to dustbins.
Boyle's smattering of screen acting roles to date include appearing as himself in the 2018 stand-up film Jellyfish and a cameo in sketch show Burnistoun. But his often misanthropic routines and apocalyptic monologues about the futility of existence could be said to echo the nihilism of Beckett's play.
"It's a proper stellar cast. We were kind of brainstorming over Endgame," Sheehan told The Times. "I thought, 'Wouldn't it be great to do this on stage after all the episodic television I've been making over so many years'.
"Then Frankie got involved when we thought about who could play Hamm. Hamm is a character who is losing his sight, he's lost the ability to walk and he's kind of losing his marbles as well. It's very funny but deeply grim and darkly comic."
Danya Taymor directs the play, which originally premiered in French in 1957, before Beckett himself translated it for English-speaking audiences.
Writing on Boyle's Instagram page, Sara Pascoe called his casting "very exciting!", to which Boyle replied: "Innit! I am also very excited that you are taking over Sewing Bee, of which I am an unlikely fan."
Last month Boyle, whose parents are Irish, revealed in an Instagram video: "I'm going to be doing something in Ireland, Dublin, but it's not stand-up. I'm quite excited about it."
He also disclosed that his long-gestating debut novel Meantime, set in Glasgow, would be published next summer. The book is about a drug addict trying to solve the murder of his friend.