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.