The vice presidential contenders - Virginia Sen. Tim Kaine and Indiana Gov. Mike Pence - were the stars of the evening as they made their cases for their respective running mates.
Here are some of the highlights of the evening's event.
Right out of the gate, Kaine introduced a line that he seemed to have been working on during his days of debate prep.
"On the economy, there's a fundamental choice for the American electorate," Kaine said. "Do you want a 'You're hired' president in Hillary Clinton or a 'You're fired' president in Donald Trump?"
Kaine continued, saying, "That's not such a hard choice," and explaining what he called their "hired plan."
Pence pounced on the line. "Well, first, let me say I appreciated the 'you're hired, you're fired' thing, senator," Pence said, dripping with sarcasm. "You used that a whole lot. I think your running mate used a lot of predone lines."
Pence continued to hit Kaine and Clinton, saying the ticket wants to "run this economy into a ditch."
Pence stood by Trump and his decision to accept a tax provision after what Pence described as "some pretty tough times 20 years ago."
Pence was asked about the recent revelations that Trump may not have paid federal income taxes for 18 years after declaring a $916 million loss in 1995, as first reported by The New York Times this weekend.
"His tax returns showed he went through a very difficult time, but he used the tax code just the way it's supposed to be used, and he did it brilliantly," Pence said.
Pence went on to praise Trump as someone who "actually built a business" and used the tax code "that actually is designed to encourage entrepreneurship."
Kaine criticized Trump for having "broken his first promise," saying Trump claimed in 2014 that he would release his tax returns if he decided to run for office.
"Gov. Pence had to give Donald Trump his tax returns to show he was qualified to be vice president. Donald Trump must give the American public his tax returns to show that he's qualified to be president, and he is breaking his promise," Kaine said.
Trump has repeatedly said that his taxes are under audit and he said that he will release them after the audit is complete.
Perhaps it was the more intimate setting, with the two candidates seated at a table within arm's length of each other rather than at lecterns. Or maybe it was the early expectation that tonight's debate would be more civil than contentious, but both candidates seemed to feel free to interrupt and talk over the other throughout the 90-minute face-off.
Kaine took an aggressive approach early on, interrupting Pence several times. And Pence followed suit.
There was so much cross-talk during an exchange over whether Trump would release his tax returns that the moderator, CBS News' Elaine Quijano, interjected, "Gentlemen, the people at home cannot understand either one of you when you talk over each other."
And again later in the debate, during another feisty exchange, Quijano pleaded for the two candidates to speak one at a time, saying, "Gentlemen, please!"
Which campaign has thrown more insults at the other side?
Pence and Kaine sparred over that question. It was clear coming into tonight's debate that Pence would be called on to defend some of Trump's more controversial comments, and tonight Kaine brought them up.
"There is fundamental respect issue here," Kaine said. "And I just want to talk about the tone set from the top. Donald Trump during this campaign has called Mexicans rapists and criminals. He's called women slobs, pigs, dogs, disgusting. I don't like saying that in front of my wife and my mother. He attacked an Indiana-born federal judge and said he was unqualified to hear a federal lawsuit because his parents were Mexican. He went after John McCain, a POW, and said he wasn't a hero because he'd been captured. He said African-Americans are living in hell. And he perpetrated this outrageous and bigoted lie that President Obama is not a U.S. citizen."
Kaine added, "I cannot believe that Gov. Pence will defend the insult-driven campaign that Donald Trump has run."
Pence fired back, calling Kaine's critique an "avalanche of insults."
"He says ours is an insult-driven campaign? Did you all just hear that? Ours is an insult-driven campaign?" Pence asked. "To be honest with you, if Donald Trump had said all of the things that you said he said in the way you said he said them, he still wouldn't have a fraction of the insults that Hillary Clinton leveled when she said that half of our supporters were a basket of deplorables."
Pence said a few minutes later, "Senator, you and Hillary Clinton would know a lot about an insult-driven campaign."
Clinton agreed with her running mate's accusation, tweeting, "Yes Trump and Pence are running an insult-driven campaign. Donald's literally doing it right now. #VPDebate," tweeting a retweet from Trump during the debate from one of his supporters, who wrote, "Kaine looks like an evil crook out of the Batman movies."
In spite of the questions that have been raised about former Trump campaign manager Paul Manafort's ties to a Moscow-backed ousted president of Ukraine and Trump's repeated praise of Russian President Vladimir Putin, Pence was the one to bring up Russia during tonight's debate.
Pence first linked Clinton's time as secretary of state to "the newly emboldened aggression of Russia, whether in Ukraine," but Quijano paused that discussion and revisited Russia when asking about the situation in Syria.
He went on to describe Putin as the "small and bullying leader of Russia" when talking about the role Russia has played in Syria. That description comes in clear contrast to Trump's praising Putin as a strong leader.
Pence said, "The provocations by Russia need to be met with American strength. And if Russia chooses to be involved and continue, I should say to be involved in this barbaric attack on the civilians in Aleppo, the United States of America should be prepared to use military force to strike military targets of the [President Bashar al-]Assad regime."
"Let me say, this whole Putin thing - America is stronger than Russia," Pence said later.
In what began as a segment with questions directed to both candidates on Syria, Kaine pivoted to attacking Trump's temperament.
"Let me tell you what would really make the Middle East dangerous: Donald Trump's idea that more nations should get nuclear weapons," Kaine argued.
"Ronald Reagan said something really interesting about nuclear proliferation back in the 1980s. He said the problem with nuclear proliferation is that some fool or maniac could trigger a catastrophic event," Kaine added.
"And I think that's who Gov. Pence's running mate is. Exactly who President Reagan warned us of," Kaine said.
"Oh, come on, senator. Senator, that was even beneath you and Hillary Clinton," Pence responded. "And that's pretty low."