The TV presenter said in a statement he is stepping down because the popular show had “become the story" and “I want to do what I can to protect the show I love”.
The 61-year-old will not return to co-host the morning talk show with Holly Willoughby, with Thursday's show being his last.
His departure comes as newspaper reports claimed his relationship with Willoughby has become strained in recent weeks.
He said in a statement posted on Instagram: “I have always been proud to cover fascinating stories on This Morning. But recently, This Morning itself has become the story.
“Throughout my career in TV - including the very difficult last few days - I have always done my best to be honourable and kind. I understand that ITV has decided the current situation can't go on, and I want to do what I can to protect the show that I love.
“So I have agreed to step down from This Morning with immediate effect, in the hope that the show can move forward to a bright future.
“I'd like to thank everyone who has supported me - especially This Morning's amazing viewers - and I'll see you all for the Soap Awards next month."
ITV said that Schofield, who has been on This Morning for more than 20 years, said the broadcaster would continue to present peak time shows for the channel, including next month's The British Soap Awards and a new prime time series.
Holly Willoughby said: “It’s been over 13 great years presenting This Morning with Phil and I want to take this opportunity to thank him for all of his knowledge, his experience and his humour. The sofa won’t feel the same without him.”
Willoughby, who has co-hosted This Morning with Schofield for 14 years, will continue on the show, said ITV, and will co-host with other members of the This Morning family.
Kevin Lygo, ITV's managing director, media and entertainment, said: “Phillip is hands down one of the best broadcasters of his generation and we thank him for his two decades worth of absolutely terrific television on the This Morning sofa.”
Schofield and Willoughby are two of the most recognisable faces on British television, and have previously been open about their close friendship.
After recent media reports of a rift, Schofield said in a statement to The Sun newspaper last week that Willoughby is his “rock".