"After eight wonderful years on The X Factor it's time for me to move on," he said in a statement.
"I'd like to thank ITV, Simon [Cowell], The X Factor family and particularly the viewers, all of whom have been a big part of my life for so long."
The 41-year-old took over from Kate Thornton in 2007 as host of the popular talent show.
The presenter and broadcaster currently presents a show on Radio 2 and recently completed a 24-hour dance challenge for Comic Relief.
"I'd like to wish the team all the best for the future, especially whoever takes over from me," O'Leary continued.
"You're about to be the conductor on the most brilliant, runaway train in showbiz. Good luck you'll love it!"
The news of his departure may fuel speculation that O'Leary is a contender to replace Jeremy Clarkson on the BBC's Top Gear.
Before Friday's announcement, William Hill had O'Leary as 6-1 to take over following the BBC's decision not to renew Clarkson's contract earlier this week.
Before The X Factor, O'Leary hosted Big Brother's Little Brother, Channel 4's companion show to its long-running reality show.
He has presented on BBC Radio 2 since 2004 and has hosted the National Television Awards since 2010.
Bookmakers Ladbrokes have made singer Olly Murs, a former X Factor runner-up, favourite to take over the vacant presenting role.
A spokesman for ITV said O'Leary had been "a fantastic host of The X Factor" and that the channel was "sorry to see him go".
"We wish him all the very best for the future and hope that he'll be back on ITV screens soon."
Dermot O'Leary will no longer host ITV's The X Factor after eight years on the programme.