The rock and roll band top the main stage on Friday, June 22, two days before Bruce Springsteen & The E Street Band close the festival.
Festival promoter John Giddings said: "We are proud to present Tom Petty and The Heartbreakers at the Isle of Wight Festival finally.
"It has taken years to achieve but I'm sure it will be worth the wait - they are one of the greatest rock and roll bands of all time."
Following Springsteen's booking, Giddings had teased the possibility of an American Trilogy of headliners while also promising more dance and urban artists on the Big Top stage.
Other acts already confirmed for next year's Isle of Wight festival include Noel Gallagher's High Flying Birds, Biffy Clyro, Example, Madness, The Vaccines and Noah & The Whale.
Watch the Tom Petty and the Heartbreakers 'Don't Come Around Here No More' music video below: