Willoughby, 42, has been on a two week half-term break following the shock departure of her former co-host and his subsequent revelation of an affair with a younger ITV male employee.
Her return to presenting duties was confirmed at the end of Friday’s episode of This Morning, which was hosted by Alison Hammond and Dermot O’Leary.
Appearing on This Morning for the first time since Schofield’s departure, on Monday, Willoughby directly addressed viewers at home and said: "Deep breath," before admitting it felt strange being on the series without her former co-host.
She began: “Firstly, are you ok? I hope so. It feels very strange indeed sitting here without Phil...
“I imagine you might have been feeling a lot like I have, shaken, troubled, let down, worried for the wellbeing of people on all sides of what's been going on. And full of questions.
“You, me, and all of us at This Morning gave our love and support to someone who was not telling the truth, who acted in a way who themselves felt that they had to resign from ITV and step down from a career they loved.
“That is a lot to process and it's equally hard to see the toll that it has taken on their own mental health,” Willoughby added.
“I think what unites us all now is a desire to heal for the health and wellbeing of everyone. I hope that as we start this new chapter and get to a place of warmth and magic that this show holds for all of us, we can show strength in each other.
“From my heart, can I say thank you for all of your kind messages and thank you for being here this morning. Myself, Josie, Dermot, Alison, Craig and every single person who works on this show will continue to work hard every single day to bring you the show that we love."
Willoughby then turned to her co-host Josie Gibson and said: “On that note...” before Gibson pulled her in for a hug.
The former Big Brother star then applauded the presenter for addressing the fallout, adding “All we can do now is be the family that we are.”
The 42-year-old’s statement comes after Schofield said he “didn’t tell anybody” about his affair with his former This Morning colleague, confirming Willoughby “did not know” in a tell-all interview with BBC’s Amol Rajan.
Similarly in his interview with the Sun, the 61-year-old presenter apologised to Willoughby for lying to her about his relationship, saying: “I’ve lost my best friend”.
He added: “I let her (Holly) down. I let that entire show down. I let the viewers down.
“Holly did not know (about the affair) and she was one of the first texts that I sent, to say: ‘I am so, so sorry that I lied to you’.
“She didn’t reply and I understand why she didn’t reply as well. So yeah, if anyone is in any way linking Holly to this, that is absolutely, wholly untrue.”
The duo, who had presented the show together since 2009 and also co-hosted Dancing On Ice before Schofield resigned from ITV, had been open about their close friendship over the years.
Willoughby’s return comes as the ITV show has been plagued by allegations of “toxicity”, including from former This Morning presenter Eamonn Holmes who has alleged there was a “total cover-up” over the Schofield affair.
This Morning editor Martin Frizell says he is not concerned about an external review over Phillip Schofield's departure, adding "I think there are scores being settled" when asked about a toxic culture at the programme.
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The show’s former resident doctor, Dr Ranj Singh, also hit out at a “toxic” culture, saying he raised concerns about “bullying and discrimination” two years ago when he worked there and afterwards felt like he was “managed out” for whistleblowing.
In a letter from ITV boss Dame Carolyn McCall to Parliament on Wednesday, she said an external review conducted following a complaint made by Dr Ranj found “no evidence of bullying or discrimination”.
Meanwhile, former This Morning head of news Emily Maddick, who worked on the show from September to December 2019, claimed she quit the programme due to “bullying, sexism and a toxic culture of fear and intimidation”.
On Saturday, This Morning editor Martin Frizell told a Sky News reporter to “read between the lines” amid claims of toxicity, adding: “I think there’s some scores being settled.”
Dame Carolyn has been called to a parliamentary committee on June 14 to answer questions about the broadcaster’s approach to safeguarding and complaint handling following Schofield’s exit.
On Wednesday, she confirmed the broadcaster had instructed barrister Jane Mulcahy KC of Blackstone Chambers to carry out an external review of the facts.