The 44-year-old is set to play the bright-but-incompetent Agent 86 Maxwell Smart in Warner Bros' take on the spy spoof, which is still in the very early stages.
Now You See Me: Now You Don't co-writer Seth Grahame-Smith is writing the screenplay, while producers include Andrew Lazar and Chuck Roven.
Mel Brooks and Buck Henry created the original Get Smart TV series in 1965, and it ran for 138 episodes until 1970, with Don Adams as Smart opposite Barbara Feldon as the capable Agent 99 and Edward Platt as Chief of the CONTROL agency.
Get Smart was then adapted for the big screen in 2008, with Peter Segal directing Steve Carrell in the title role alongside the likes of Anne Hathaway, Dwayne Johnson, Alan Arkin and Terence Stamp.
Mulaney was most recently seen as the host of Netflix's Everybody's Live with John Mulaney in 2025 and he's preparing to kick of a run of nine comedy shows in January.
His next movie role will be as Electronic Arts founder Trip Hawkins in David O. Russell's sports biopic Madden.
Meanwhile, Mulaney previously joked that a "star-studded intervention" helped to save his life.
The comedian sought treatment for alcoholism and cocaine addiction back in 2020, and John joked about his recovery in his Netflix comedy special, John Mulaney: Baby J.
The TV star - who has Malcolm, four, and Mei, 23 months, with wife Olivia Munn - said: "Let me just call this out now, I don't mean to be weird. It was a star-studded intervention. It was, like, a good group."
The former Saturday Night Live writer joked he was flattered by the star-studded line-up for his intervention.
He quipped: "It was a good group. As mad as I was when I walked in there, I was like, this is a good line-up, this is really flattering in its own way.
"It was like a We Are the World of alternative comedians over the age of 40. All comedians. Yet no one said a funny thing the entire night."
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