They include Harry Potter author JK Rowling, Sherlock Holmes actor Benedict Cumberbatch and former James Bond star Roger Moore.
The move marks a U-turn for festival bosses, who last year dropped the 2,200-seater Centaur and a host of other big venues in favour of centralising the event within the bounds of Montpellier and the town hall.
They claimed at the time it was "not a quality experience" for festival goers to have to trek across Cheltenham from venue to venue.
However, executive director Jane Furze promised drawing crowds away from the festival's heart would not detract from the vibrant atmosphere.
"We are committed to developing the festival quarter in the gardens and creating buzz in the town centre," she said.
"Every year we review how we use venues throughout the town to create the best festival experience. This year, in addition to the venues in the festival quarter, we're using the Centaur at Cheltenham Racecourse for a day of high profile events.
"It is the town's largest venue, and is a great setting for such outstanding speakers as JK Rowling, Benedict Cumberbatch (whose event will be chaired by Sherlock's Louise Brealey) and Michael Palin.
"By using it alongside the festival quarter we are able to offer our audiences the chance to see some of the world's highest profile speakers."
More than 600 of the world's leading writers, thinkers, actors, politicians, comedians and wits will feature at the festival, which takes place between October 5 and 14.
A star-studded lineup will appear at the Centaur on October 6, including Hercule Poirot actor David Suchet and TV personality Palin as well as big hitters Rowling, Cumberbatch and Moore.
Racecourse director Edward Gillespie said he was delighted to welcome events back after not featuring last year.
"We are thrilled to be playing a part in this year's literature festival," he said. "The Centaur is a fantastic venue which can accommodate the kind of crowds you couldn't get anywhere else in Cheltenham.
"We hope that after hosting events on one day of the festival this year, down the line we could get to the stage where we are hosting two or three days."
Tickets go on sale to Cheltenham Festivals members on Monday, ahead of booking opening to the public on August 20. The full line-up can be viewed at www.cheltenhamfestivals. com/literature-brochure-2012
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The thought of Rowling, Palin and Cumberbatch in the same place alone would have made it worth it, sobbing @this being out of my reach rn.