Clinton parried the assault with a scathing attack on the GOP nominee as a greedy misogynist and bully, who used his public prominence to personally enrich himself, take advantage of women and exploit employees of his lucrative business empire.
She said she found "horrifying" the intimation he would not accept the will of the people on Nov. 8.
After a fairly placid start, in which they differed over guns, Supreme Court appointments and taxes in a relatively civil tone, the debate turned into an angry flood of innuendo and insult, starting when Trump defended himself against allegations he had repeatedly forced himself on women.
Trump categorically denied the charges, which have dominated the campaign in the last week, and asserted without proof that the Clinton campaign had orchestrated the statements from more than half a dozen women who came forward to accuse Trump.
"These stories are all totally false," he said firmly. "I didn't know any of these women — I didn't see these women…. I think they want either fame or her campaign did it, and I think it's her campaign."
Clinton, speaking slowly and deliberately into the television camera, noted that Trump had earlier denied the allegations, in part, by suggesting the women were not attractive enough to draw his interest.
"Donald Trump thinks belittling women makes him bigger," Clinton said. "He goes after their dignity, their self-worth, and I don't think there is a woman anywhere who doesn't know what that feels like."
"I think it's really up to all of us to demonstrate who we are," she went on, "and who our country is, and to stand up and be very clear about what we expect from our next president."
Trump simply repeated his contention that the various accounts were false.
"Nobody has more respect for women than I do," he said.
The 90 minutes onstage at the University of Nevada, Las Vegas, represented Trump's last, best chance to stop a drastic political slide and keep the White House in reach. He used the opportunity to repeatedly disparage Clinton's character and personal integrity.
"Such a nasty woman," he uttered at one point.
"This is just another lie," he said at another.
He suggested the Democrat would continue what he described as the failed domestic and foreign policies of
"The one thing you have over me is experience," he said, "but it's bad experience. The problem is you talk but you don't get anything done, Hillary. If you become president this country is going to be in some mess, believe me."
Clinton countered that she had spent her entire career working to help the poor, children and minorities while Trump was accumulating personal wealth. While she was in the White House Situation Room, as secretary of State monitoring the raid that killed Osama bin Laden, "he was hosting the 'Celebrity Apprentice,'" she scoffed.
"So I am happy to compare my 30 years of experience," she said.
Under the intended format, Wednesday night's debate was sectioned off in 15-minute intervals devoted to topics chosen by the moderator, Fox News anchor Chris Wallace. For roughly half an hour, that managed to corral the candidates.
They differed over Supreme Court appointments, Clinton saying she would appoint justices who uphold legalized abortion, same-sex marriage and rein in unlimited political contributions.
Trump said he would appoint justices that would overturn the 1973 Roe vs. Wade decision that legalized abortion and would strictly uphold expansive gun rights.
But Trump has shown a penchant — on the debate stage and, especially, at his boisterous rallies — for straying far afield from policy and typical campaign discourse, and he did so again Wednesday night.
In a striking breach of the country's long-standing tradition, he twice declined when pressed to say whether he would accept the outcome of the election. "I will look at it at the time," Trump said. "I'll keep you in suspense."
There was a gasp from the audience inside the debate hall.
"That is not the way our democracy works," Clinton said. "He is denigrating, he is talking down our democracy. And I for one am appalled that somebody who is the nominee of one of our two major parties would take that kind of a position."
In a discussion of immigration, Trump accused Clinton of favoring amnesty for millions of people in the country without proper documentation, calling that unfair to those who entered the country properly. "We either have a country or we don't," said Trump, whose signature issue is construction of an impenetrable wall along the U.S.-Mexico border.
At one point, the GOP nominee, who is highly unpopular among Latinos, tossed in a word of Spanish as he vowed to rid the U.S. of drug lords and other "bad, bad people" who entered the country illegally. "We have some bad hombres here, and we're going to get them out," he said.
Clinton said she favored tough border security but not going "school to school, home to home, business to business rounding up people who are undocumented," as she said Trump's policy would require.
The first two debates have proved to be pivot points in the contest, turning a race that favored Clinton into a potential blowout. Her lead in polls has grown, both nationally and in states Trump needs to win. Even some traditionally Republican states, such as Arizona, Georgia and Utah, have grown competitive in the final weeks of the contest.
Trump's response has been to assert, without proof, that a collection of conspirators — Clinton, the media, international financiers and fellow Republicans, including House Speaker Paul D. Ryan — are trying to steal the election.
But his earlier performances on the debate stage contributed greatly to his problems.
An ill-prepared Trump was tetchy and erratic in last month's first session, then compounded his troubles by spending days on a body-shaming campaign against a former Miss Universe whom Clinton had defended.
Subsequent revelations — that Trump may have avoided federal income taxes for close to two decades and bragged in a 2005 videotaped conversation that his celebrity allowed him to force himself on women — dominated the second debate.
Trump's insistence in the last debate that he never acted inappropriately was the cause for several women to step forward and accuse him of unwanted sexual advances.
Trump's difficulties have overshadowed developments that could have been harmful to Clinton, including a series of hacked private emails of her campaign chairman that portray the candidate in less-than-flattering ways and new details concerning her private email server.
A question from Wallace about the hacking — which U.S. intelligence officials have blamed on Russia — led to a harsh exchange over Trump’s professed admiration for Russian President
Clinton accused Trump of accepting the help of Russian operatives believed to have hacked the documents and giving them to WikiLeaks to try to influence the American election. Clinton demanded that Trump "make it clear he will not have the help of Putin in this election, that he rejects Russian espionage against Americans."
Trump accused Clinton of trying to deflect the discussion away from another of the WikiLeaks disclosures. She had been asked about a document that showed her telling a group of bankers during a paid speech that she supported a "hemispheric common market with open trade and open borders."
"That was a great pivot off the fact that she wants open borders," Trump said. "I don't know Putin. He said nice things about me. If we got along well that would be good…. He has no respect for her, he has no respect for our president, and I'll tell you what, we are in very serious trouble."
Clinton shot back: "That's because he'd rather have a puppet as president of the United States," referring to Putin's praise of Trump.
"You're the puppet," Trump responded.
A discussion of the economy centered on the candidate's respective tax plans. Clinton charged that Trump would give "the biggest tax breaks ever to the wealthy and to corporations" and cited analyses that it would reduce employment overall.
Trump accused Clinton of proposing a "massive, massive tax increase" before turning to what has proved to be more comfortable terrain: trade. He vowed to work to renegotiate the
Clinton defended her tax plan, reiterating a pledge not to raise taxes on anyone making $250,000 or less but seeking higher taxes from wealthier Americans that would allow her to make investments in new jobs and innovation. She also reiterated her opposition to the Trans-Pacific Partnership, a proposed 12-nation agreement championed by Obama, and said she would aggressively enforce existing trade agreements.
Before the debate, both campaigns engaged in a bit of psychological gamesmanship.
Trump announced his guests would include the mother of an American killed in the 2012 attacks on the U.S. diplomatic outpost in Benghazi, Libya, as well as Obama's Kenyan half-brother, Malik. Clinton’s guests included billionaire Mark Cuban, a longtime Trump detractor, and Hewlett Packard Enterprise Chief Executive
Trump and Clinton may share a stage one more time before election day on Nov. 8. The antagonists were both scheduled to attend the 71st annual Alfred E. Smith memorial dinner Thursday night in Manhattan, a traditionally lighthearted affair that raises funds for Catholic charities.
Barabak reported from San Francisco, Halper from Las Vegas and Memoli from Washington.
9:45 p.m.: This story has been updated with additional comments from the debate and for clarity.
8:25 p.m.: This story was updated with comments from the debate.
6:10 p.m.: This story was updated with the start of the debate.