The presenter, 53, accused Meghan of “ghosting” him and “sacking him like a sack of spuds” after meeting someone “more important”.
Piers was discussing a string of negative stories about Meghan which accused her of making Kate Middleton cry and emailing staff at 5am.
The US actress also allegedly complained about the smell of St George's Chapel at Windsor Castle and Prince Harry is believed to have shouted: “What Meghan wants, Meghan gets.”
Speaking on Good Morning Britain, Piers today described the 37-year-old as being a “piece of work”.
He also said he put her "in the cab to Harry to start with" but said he "never heard from her again" after she met him.
Piers added: “I’ve had my own experience with her, which was not great to be honest. I knew her for about a year and a half.
“I got on really well with her and then “bang” she met someone more important and immediately ghosted.
“I never heard from her ever again and the old slippery slope ladder had gone up and she social climbed her way out of my orbit.
“So my experience wasn’t great, I’ve got to be honest with you. And everything I’ve seen since does slightly smack of an actress, a Hollywood actress, seizing her chance and acting her way to the top.”
But journalist Radhika Sanghani hit back and described Piers’ comments as being “absolutely ridiculous”.
She said: “As a normal person, to me it is this really lovely love story between them.
“When you saw their wedding it was very obvious they were in love and they seem a great married couple.
“But unfortunately, with this media narrative we’re seeing now, it’s completely changed.”
Author Tom Bower, who wrote a book on Prince Charles, said Meghan is a “victim of her own ambition”.
He said: “I don’t think anyone is out to get her, I think she’s a victim of her own ambition.
"People are unhappy – they always leak. That’s what Piers and I live on – the victims, coming forward and confessing their unhappiness.
“She’s trying to be Diana, trying to adopt the new role. The tragedy is that it will end in the same way unless someone steps in from the palace and says this is the way it’s done here.”
Piers also said Meghan is very different to Kate Middleton, who he described as being "very home counties" and "safe".
He added: "Kate Middleton is very “home counties” and safe, almost groomed for the role – it’s much easier for everybody to have that kind of person.
“Meghan is from a very different background, a TV star, and probably finds the Palace system very suffocating and annoying.
“And the people around her like the formality of it and probably equally find her annoying.”
Mr Bower added: “The problem is there’s never been in the Palace someone who can step forward and say look Meghan, this is how you may have done it in Hollywood, but here in London we do it this way."
Speaking to Radhika, he said: "The problem is that the argument you’re putting forward is that she’s living in a goldfish bowl.
“You wrote that she deserves privacy. She doesn’t, she’s on public display and when you’re on public display 24/7 there’s a certain way of behaving.”
Piers added: “You can’t go after a prince as she did. And I know she did. I put her in the cab to Harry to start with.
“You can’t set your sights on a prince to this country who is in line to the throne and expect to have a normal private life afterwards.
“It’s part of the deal. To live in Palaces at our expense you get to be in the papers. Good, bad and ugly.
“I would say predominately positive coverage, a few negative stories recently.
“I would say there are concerns in the Palace over her treatment of her father. It’s probably an ongoing massive issue. For a woman to just cut her father off.
“From the moment she met Harry she ditched anyone who could have been a problem.
“The two most consistently beloved people in the royal family are the queen mother and the queen.
“What is the most common denominator? They’ve never given an interview and they don’t’ respond to criticism and they don’t’ engage in day to day headlines. They rise effortless and regally above it all.
"The queen is the most revered person in the world you could argue and she’s done so by saying nothing in public and behaving like a royal.”
Ms Sanghani said: “But what Meghan is doing is inspiring a generation and being different and being fresh and I’m a massive fan.”
Piers added: “Well she didn’t inspire me, she sacked me like a sack of spuds. Take people as I find them, and I wasn’t impressed.
“If you’re watching Meghan – I’m not happy.”
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