But Mr Trump's female supporters are maintaining their support for him, and he has threatened to sue over fresh sexual-harassment claims he dismisses as fabrications.
She may have mentioned him only as the presidential candidate, but there was no doubting who was the subject of Michelle Obama's denunciation.
"This is not something that we can ignore, not something that we can just sweep under the rug as just another disturbing footnote in a sad election season. And I have to tell you that I listen to all this and I feel it so personally, and I'm sure than many of you do, too, particularly the women. The shameful comments about our bodies, the disrespect of our ambitions and intellect, the belief that you can do anything you want to a woman? It is cruel. It's frightening. And the truth is it hurts."
The wife of United States president Barack Obama was speaking at a rally in support of Democratic nominee Hillary Clinton.
She was responding to the widely publicised video that has emerged from a decade ago, showing Donald Trump bragging about groping women.
"This was not just a lewd conversation. This wasn't just 'locker-room banter.' This was a powerful individual speaking freely and openly about sexually predatory behavior and actually bragging about kissing and groping women, using language so obscene that many of us were worried about our children hearing it when we turn on the TV. And to make matters worse, it now seems very clear that this isn't an isolated incident."
In the latest controversy to haunt the Republican nominee's campaign, former sales executive Jessica Leeds has come forward to detail an alleged encounter with him on a plane.
She says the billionaire businessman was sitting next to her in first class on a flight to New York 35 years ago.
"I hesitate to use this expression, but I'm going to, and that is he was like an octopus. It was like he had six arms. He was all over the place. If he had stuck with the upper part of the body, I might not have gotten that upset. But it was when he started putting his hand up my skirt, and that was it. That was it. I was out of there."
But speaking at rally in the state of Florida, Mr Trump has denied the allegation and others that surfaced in recent days.
"These claims are all fabricated. They're pure fiction, and they're outright lies. These events never, ever happened, and the people that said them meekly fully understand. We already have substantial evidence to dispute these lies, and it will be made public in an appropriate way and at an appropriate time, very soon."
Earlier, as his lawyers threatened to sue the media, Mr Trump took to Twitter to question the timing of the allegations.
They also included claims he forcibly kissed a journalist while she interviewed him for a profile.
"Why didn't the writer of the 12-year-old article in People Magazine mention the incident in her story? Because it did not happen!"
The New York Times is standing by its story, but Mr Trump's female supporters at the Florida rally were unmoved by the claims.
"Now what I'm saying is that Donald Trump is running for president, not to be the next pope, so, come on, you know, stop it already."
"I don't care. Nobody cares. The way Mr Trump handles his personal life and what he does is his business. It's not going to affect me."