Jackson, who took up the post in February 2006, has overseen some of ITV's most successful shows including 'Britain's Got Talent', 'The X-Factor' and 'Dancing on Ice'.
He joined ITV following a five-year stint in Australia, 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.
Prior to that, Jackson was controller of entertainment at the BBC, responsible for entertainment content across all platforms.
Jackson said: "I have totally enjoyed my time working for Simon [Shaps] and, more recently for Peter [Fincham], 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.
"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's resignation comes almost four months after Peter Fincham was appointed director of television at ITV in May.
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."
ITV has not yet made a decision on Jackson's replacement.