In a statement, he said: “I understand ITV has decided the current situation can’t go on.”
His departure comes after reports claimed relations between him and co-host Holly Willoughby had come under strain in recent weeks.
Willoughby said: “The sofa won’t feel the same without him.”
She will remain as a presenter on the programme, and will be joined by “members of the This Morning family”, ITV said, while confirming Schofield’s Thursday appearance was his last.
Schofield will continue working with the broadcaster, ITV’s statement added, saying this included The British Soap Awards in June and a “brand new peak time series to come”.
On Instagram, Schofield wrote: “Throughout my career in TV – including in 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.”
In a statement on Instagram, 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.”
Kevin Lygo, ITV’s managing director, media and entertainment, called Schofield “one of the best broadcasters of his generation” and thanked him for “two decades worth of absolutely terrific television”.
Schofield has been a regular presenter on This Morning since 2002, and Willoughby since 2009. The pair also present ITV’s Dancing On Ice together.
After reports of a “cooling” in the pair’s friendship appeared in The Sun earlier this month, Schofield told the newspaper: “The last few weeks haven’t been easy for either of us.”
But he said his co-host was his “rock”, adding: “She is an incredible support on screen, behind the scenes and on the phone.”
Willoughby will take an “early half term holiday”, ITV said, and will return to screens on 5 June.
Schofield recently returned to the show after taking pre-planned leave around his younger brother’s sex abuse trial at Exeter Crown Court.
Timothy Schofield was jailed for 12 years on Friday for 11 sexual offences involving a child between 2016 and 2019.
Phillip Schofield first found fame on children’s TV in the 1980s on the BBC’s Broom Cupboard, and then on Saturday morning show Going Live!
He starred in West End productions and fronted TV game shows like Talking Telephone Numbers and Schofield’s Quest before joining This Morning.
The programme has won a host of awards, including the prize for best daytime programme at last year’s National Television Awards.
While their on-screen relationship may have won plaudits and attracted audiences, Schofield and Willoughby were criticised in September last year over claims – which they denied – that they skipped the queue for the Queen’s lying-in-state while attending to film a segment.
Willoughby also took time away from the show in April after she contracted shingles.