Donald Trump was likened to a "fool or maniac" while Hillary Clinton was dismissed as "weak and feckless" in a punchy vice-presidential debate.
Democratic Virginia Senator Tim Kaine and Republican Indiana Governor Mike Pence clashed on a series of topics ranging from abortion to Russia.
But they focused their sharp exchanges on Mrs Clinton and Mr Trump.
The running mates tangled at Longwood University in Farmville, Virginia, 34 days before Americans go to the polls.
It set the stage for a second presidential debate this Sunday in St Louis, Missouri, between Mrs Clinton and Mr Trump, who needs to rebound from a wobbly performance in their first match.
In Tuesday's 90-minute duel, the usually low-key Mr Kaine went on the attack from the beginning.
But while the two frequently talked across each other, Mr Pence was unruffled.
Mr Kaine invoked Republican President Ronald Reagan when talking about the dangers of nuclear weapons under a Trump presidency.
He said Mr Reagan had once warned that nuclear proliferation could lead to "some fool or maniac" triggering a "catastrophic event".
Mr Kaine said the Republican commander-in-chief had been referring to someone like Mr Trump.
The 58-year-old senator also criticised Mr Trump's temperament, saying he "can't start a Twitter war with Miss Universe without shooting himself in the foot".
In one of the more heated moments, Mr Kaine sharply criticised Mr Trump's complimentary remarks about Russian President Vladimir Putin.
Mr Trump praised dictators, said Mr Kaine, and had a "personal Mount Rushmore" made up of Mr Putin, Kim Jong-un, Saddam Hussein and Muammar Gaddafi.
"If you don't know the difference between dictatorship and leadership, then you've got to go back to a fifth-grade civics class," Mr Kaine said.
But 57-year-old Mr Pence contended Mr Putin would respect Mr Trump because of his strength, "plain and simple".
He added that "the small and bullying leader of Russia has been stronger on the world stage than this administration - that's stating painful facts".
That's not an endorsement of Mr Putin, he said. "That's an indictment of the weak and feckless leadership of Hillary Clinton and Barack Obama."
The two candidates also clashed on Mr Trump's tax arrangements, which have come under scrutiny in recent days.
The property tycoon has refused to release his tax returns, but the New York Times reported he may have avoided paying taxes for the last 18 years.
Mr Pence said his running mate had "used the tax code just the way it's supposed to be used, and he did it brilliantly".
Mr Kaine shot back: "I guess all of us who do [pay taxes] are stupid?"Other debate highlights:
Mr Pence said Mrs Clinton should "stop seizing on these moments of tragedy" over
police shootings, but Mr Kaine shot back: "I can't believe you are defending the
position that there's no (police) bias"
Mr Kaine said the Trump campaign was "insult-driven", but Mr Pence hit back that it was
"small potatoes" compared with what Mrs Clinton has said about the Republican
Mr Pence said the US should use military force to target Syrian government targets if
Russia continues to support its "barbaric attack" on Aleppo
The two pro-life candidates also clashed over Mr Trump suggesting women should be
punished for having abortions. Mr Pence chalked it up to Mr Trump's inexperience:
"Look, he's not a polished politician like you and Hillary Clinton"
The debate was hosted by CBS News' Elaine Quijano and followed last week's presidential debate, which drew a record 84 million viewers, according to Nielsen.