The Scottish National Portrait Gallery will exhibit a collection of his portraits during the festival period in Edinburgh next summer.
Byrne, the creator of Tutti Frutti and The Slab Boys trilogy as well as murals and paintings, is being honoured by the show for his "contribution to Scottish art".
Works in the exhibition, which will feature around 50 paintings, include a portrait of his former partner, the award-winning actress Tilda Swinton, the actor Robbie Coltrane, and a self portrait which currently hangs in the Portrait Gallery's cafe.
Byrne, who was born in 1940 in Paisley, attended Glasgow School of Art between 1958 and 1963 and has long been known for his portraiture.
Christopher Baker, director of the Scottish National Portrait Gallery, said: "We are delighted to be working closely with John Byrne on this exciting project for next summer which will bring together around 50 key works, from drawings to large-scale paintings. We are sure this show will be a huge draw for both fans of John's artwork, and those who know him in one of his many other artistic guises."
As well as a writer and artist, Byrne is a designer, having once designed book jacket covers, record sleeves, and theatre backdrops.
He recently wrote a version of Chekhov's The Cherry Orchard and is also known for writing the TV series Your Cheatin' Heart.
The artist said: "It is very lovely news. It is my first show at the National Galleries, and it will run alongside an exhibition of new work at Bourne Fine Art Gallery."
Tomorrow Mr Byrne is at an event at the portrait gallery in a session with the author AL Kennedy, as his portrait of Billy Connolly is featured in the current exhibition Tickling Jock, the exhibition which celebrates Scotland's comedy "greats".
Byrne recently unveiled a mural on the dome of the auditorium at the King's Theatre in Edinburgh.