The band will celebrate the tenth anniversary of their second studio album Origin Of Symmetry at the music event, which takes place between August 26-28.
Frontman Matt Bellamy told NME: "It's always been an album the hardcore fans have always talked about as one of their favourites, if not the favourite. So we wanted to play it for them as a celebration of the ten years since it came out."
Bellamy explained that the performance will include a new stage show and production based around the concept and artwork of the album, saying: "We'll do whatever we can get away with within the restrictions of a festival stage."
Drummer Dom Howard added: "We'll probably just do the old cheap encore and play a few hits!"
My Chemical Romance, Pulp and The Strokes will also play headline slots at the rock festival this weekend.
Other acts confirmed to play include Beady Eye, The National, Elbow, Two Door Cinema Club and Metronomy.
Watch Muse perform 'Feeling Good' live at Reading Festival in 2006 below: