The motormouth star is stepping into Chris Tarrant's shoes for a week-long run of the show which is celebrating its 20th anniversary.
Clarkson will host seven new episodes over the space of a week.
The popular show first arrived in September 1998 with the final episode airing in February 2014.
When asked about his new job, Clarkson said: "I have always loved the show and am thrilled to be involved with its rebirth.
"I'm a big fan of quiz shows and I'm looking forward to hosting this iconic TV show and hopefully making a few millionaires!"
Who Wants To Be A Millionaire kicks off this Saturday, May 5 at 9.15pm and will run until May 11.