With less than four weeks before Election Day, and Clinton maintaining her edge in national polls, the pair bore down on key battleground states where the race is likely to be decided.
Trump slammed his opponent, declaring her a criminal who should be prosecuted for endangering national security by using a private email account while secretary of state, and deleting some 33,000 messages that Clinton said were personal and not work-related.
"After getting the subpoena to give over your emails and lots of other things, she deleted the emails," a fired-up Trump told supporters in Lakeland, Florida.
"She has to go to jail," he added, to rousing cheers.
"Based on her crimes, she should not be allowed to run for president. It's time for a new direction," he said, to chants of "Lock her up!" from the crowd.
Trump made similar remarks hours earlier in Ocala, another city in the crucial central region of Florida near Orlando.
"Whether I win, lose or draw, I'm ashamed of what's happened to our country, and so are you," he said.
Trump is facing intense outside opposition and a wave of anger from fellow Republicans for vile remarks he made about women that were caught on a hot mic in 2005, and made public last Friday.
With his support teetering, the candidate appeared ready to unleash scorched-earth tactics against Clinton, as he did to a degree in their second debate on Sunday, when he reminded the nation of former president Bill Clinton's infidelities and threatened to appoint a special prosecutor to investigate Hillary Clinton if he wins the election.
He also went negative once more on Paul Ryan, after the House speaker told fellow Republican lawmakers that he could no longer defend or campaign with Trump.
"Already the Republican nominee has a massive disadvantage and especially when you have the leaders not putting their weight behind the people," Trump said, angry that Ryan failed to congratulate him for his debate performance against Clinton Sunday.
'Sinister deal'
"You'd think they'd say great going Don, let's go. Let's beat this crook," Trump said.
"No, he doesn't do that," he added of Ryan. "There's a whole sinister deal going on."
Clinton sought to strike a more positive tone to her supporters in Colorado to counter the Trump effort to turn off voters.
"I want to give you something to vote for, not just something to vote against," she said in Pueblo, dismissing Trump's assaults as "desperate."
"That's all they have left. Pure negativity, pessimism, and we're not going to let Donald Trump get away with it, are we?" she said.
"America is better than what Donald Trump says and represents."
She also cast an eye to potentially expanding the electoral map in her favor, after new polling came out showing that races in traditionally Republican bastions Utah and Arizona were in play.
"If you've got any friends in Utah and Arizona, make sure they vote too," Clinton said.
Trump meanwhile blasted her for comments she apparently made in closed-door speeches to Wall Street banks and other corporations in recent years, after portions of the speeches were made public when anti-secrecy group WikiLeaks published hacked emails to and from Clinton staffers.
"She pledged to dissolve the borders of the United States of America," Trump fumed.
Clinton apparently told a Brazilian bank in 2013: "My dream is a hemispheric common market, with open trade and open borders, sometime in the future with energy that's as green and sustainable as we can get it."
Clinton's campaign has expressed concern that Russian hackers are to blame for the cyber-attacks on her campaign's emails.
The Federal Bureau of Investigation has determined that Russian intelligence agencies are behind the hack of Clinton campaign chairman John Podesta's email account, according to the Wall Street Journal.
"This level of meddling by a foreign power can only be aimed at boosting Donald Trump and should send chills down the spine of all Americans, regardless of political party," Podesta said in a statement.