The special comeback will be part of Channel 4's Stand Up To Cancer charity fundraising campaign in October.
Former Doctor Who actor David Tennant had been rumoured as a potential host before Merchant was confirmed.
The cult show originally ran from 1990-95 and was first hosted by Rocky Horror Show creator Richard O'Brien and then Ed Tudor-Pole in its last two years.
Merchant is best known for writing and acting with Ricky Gervais on TV comedies The Office, Extras and Life's Too Short.
He said: "As a huge fan of the original series, I'm honoured to support Stand Up To Cancer by hosting this one-off edition of The Crystal Maze.
"Richard O'Brien and Ed Tudor-Pole leave big shoes to fill, but I have size 14 feet, so I'll do my best."
The Crystal Maze saw members of the public tackle a range of physical, mental, skill and mystery timed challenges across four themed zones.
The format was recently revived as an immersive live experience in London thanks to a crowdfunded project.
The celebrity contestants for the new TV incarnation are yet to be revealed.
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Comedian Stephen Merchant is to host a one-off celebrity revival of 1990s game show The Crystal Maze for charity.