Eamonn Holmes has described Phillip Schofield as "delusional" and said he has "picked the wrong person... if you're looking for a fight".
He was responding after Schofield, 61, released a statement attacking his critics as "a handful of people with a grudge against me".
He rejected accusations of "toxicity", describing those working or appearing on the show as "a family of wonderful, talented, kind, hard working people".
"In all the years I worked there there was no toxicity," he added.
Holmes, 63, who used to cover for him on This Morning, called him a "liar" and said he was "reluctant to give the liar any more publicity".
"But believe me Pip if u r looking for a fight , u have picked on the wrong person," he wrote.
Hours later, Holmes doubled down, saying, "A lie unchallenged becomes the Truth ... not on my watch it doesn't Pip" and accusing Schofield of "controlling , coercive behaviour".
ITV has been forced to answer questions about how much it knew about the relationship and accusations of a "toxic" culture. Bosses have confirmed they investigated rumours in 2020 but both parties denied it.
'We happen to be in the news at the moment'
Alison Hammond and Dermot O'Leary, who have presented This Morning since Schofield stepped down, made brief reference to the controversy on Monday's edition.
"We happen to be in the news at the moment, and of course we appreciate that," O'Leary said ahead of their newspaper review.
"But just from both of us and the whole team here, the crew, the guys downstairs, we love making this show for all of you."
Hammond added: "We really do. And that's exactly what we're going to do."
Gyles Brandreth, who was reviewing the papers, also offered his support, saying: "This is a happy place to work. I enjoy coming here."
'Toxic culture' goes 'far beyond' Schofield
It comes after former This Morning doctor Ranj Singh, released a statement about the "toxic culture" at the show, claiming the "issues" with it "go far beyond him [Schofield]".
He said he "took my concerns directly to the top of ITV", but nothing came of it.
"There are some good people in TV, but we need to be brave and stand up to those who aren't. Even if it's scary as hell, we have to do the right thing otherwise nothing will change," he wrote.
ITV said it was "saddened" to hear Dr Ranj's comments, but that his complaint was investigated and "no evidence of bullying or discrimination" was found.
Eamonn Holmes also tweeted on Friday to say Schofield had "finally been caught out".
"He's not the only guilty party. 4 high members of ITV management knew what sort of man he was," he said.
Schofield originally said he was stepping down from This Morning because it had "become the story", following reports of a feud between him and co-host Holly Willoughby.
It came after his brother was recently jailed for 12 years over child sex offences.
Willoughby, 41, is due to return next Monday (5 June), having gone on an early half-term holiday on 22 May.
She said that "when reports of this relationship first surfaced, I asked Phil directly if this was true and was told it was not".
"It's been very hurtful to now find out this was a lie," an Instagram statement added.
Schofield has now completely resigned from ITV and been dropped by his agents.
In his statement to the Daily Mail he also admitted lying about his affair to his wife, to ITV, his agents and the media.
The controversy has raised doubts about both Willoughby's and the show's future, but the channel has denied reports it could be axed.