The British band will top the bill for the third time at the two festivals following previous headline performances in 2011 and 2006.
Last year Muse made it a hat-trick of Glastonbury headline slots as they played the Pyramid Stage.
The band - fronted by Matt Bellamy - are to be joined by fellow Brits Bastille as well as electronic dance group Major Lazer and American hip hop artist Danny Brown.
Muse said they were “very excited” to be playing the Leeds and companion Reading festivals again.
A festival organiser added: “I’m thrilled to be able to announce Muse as the first headliner for Reading and Leeds 2017.
“Their incredible live show promises to be an unforgettable performance - we have so much more to announce and I can’t wait to reveal the rest of the line up.”
Brown’s appearance comes on the back of his distinctive fourth album that was released earlier this year to wide acclaim.
Also confirmed are US group At The Drive-In, Canadian breakout star Tory Lanez, British indie rockers Glass Animals with hundreds more acts still to be announced.
Reading and Leeds Festival 2017 will run simultaneously between August 25 and 27.