In a statement, the former British number one tennis player announced that he is to leave the show in the autumn.
"I have had a fantastic ten years fronting one of the UK's most-watched television programmes, but with all the changes taking place at GMTV I felt it was time for a new chapter in my life as well," he said.
"I enjoyed both meeting and working with some very talented people at the programme and I wish all those at GMTV every success in the future."
Alison Sharman, director of factual, daytime and GMTV, thanked Castle for the work he has done over the last decade.
"He has been a vital and central part of the presentation team. And now he has decided to move on, I wish him good luck and best wishes with all the new projects that he will be taking on," she said.
The 46-year-old, who will present his last show in early September, will return to ITV later in the year as presenter of peaktime entertainment series 71 Degrees North.
Ben Shephard and Penny Smith have also quit GMTV amidst a shake-up that will see Adrian Chiles take over the main presenting duties five days a week.