His departure follows months of speculation that he would leave the broadcaster, and ITV is now "considering all options" about how and if it should replace him.
ITV director of television Peter Fincham said: "Paul is a legend in the entertainment and comedy world. He committed to the role for three years and has commissioned and overseen some of the network's biggest and best programmes, including Britain's Got Talent and Benidorm, while taking Dancing on Ice and The X Factor from strength to strength. I am very grateful for his support and look forward to working with him in his next venture."
Jackson said: "I have totally enjoyed my time working for Simon [Shaps] and, more recently for Peter, an old friend for whom I have the greatest personal and professional respect.
"We have had a challenging and exciting ride since the new entertainment and comedy team came together and it has been a blast to work with some of the best professionals you will find in UK television.
"We have built on ITV's reputation as the home of the stars, with Neil Diamond, Take That, Girls Aloud and Paul McCartney all featuring in our schedules this year. I am leaving a great team with a very full slate of hit shows and a few new ones to play out in the coming months. It's been a fabulous experience, which I wouldn't have missed for anything."
Jackson took up the post in February 2006 following a five-year stint in Sydney, where he was managing director of Granada Media Australia and chief executive of Red Heart Productions, Granada's Australian production join venture with Seven Network.
Before leaving for Australia in 2000, Jackson was controller of entertainment at the BBC, responsible for entertainment content across all platforms.
Other high points of Jackson's career include being the launch managing director of Carlton and a key member of the management team which wrote its successful application for a London weekday franchise.
His production credits include sci-fi sitcom Red Dwarf, and Bafta-winning series 3 Of A Kind and The Young Ones. More recently he has executive produced the US versions of Hell's Kitchen and Nanny 911 for Fox.
There is already speculation that ITV may not replace Jackson directly. If it does, BBC entertainment controller Elaine Bedell, who worked with Fincham at the BBC, is being talked about as a frontrunner.
Other potential candidates would include entertainment veteran John Kaye Cooper, who in April left his job as creative director of Talent TV to become ITV controller of entertainment.