Trump tweeted in support of Pence saying he is, "doing GREAT" and Harris, calling her a "gaffe machine," a criticism he uses often to attack her running mate Joe Biden.

Biden has also tweeted in support of his running mate during the debate, saying that Harris is "showing the American people why I chose her as my running mate."

In speaking to American leadership, Pence brought up the case of Kayla Mueller, a humanitarian worker from Arizona who was kidnapped by the Islamic State in Syria in 2013 and died in the terror group's custody.

Mueller's parents were in the debate's audience as Pence's guests and appeared last month at the Republican National Convention.

Pence suggested former President Barack Obama and Biden carried blame for Mueller's death, saying they "hesitated for a month" while she was held captive.

Harris, in her response to the topic of American leadership, first addressed Mueller's family.

"First of all, to the Mueller family, I know about your daughter's case and I'm so sorry. I'm so sorry. What happened to her is awful and it should have never happened," Harris said. "And I know Joe feels the same way. And I know that President Obama feels the same way."

In a discussion of foreign policy and the role of American leadership, Harris brought up Trump’s handling of the Iran nuclear deal and criticized the president's “unilateral” approach.

“He's walked away from agreements,” she said. “We were in the Iran nuclear deal with friends, with allies around the country. And because of Donald Trump's unilateral approach to foreign policy, coupled with his isolationism, he pulled us out and has made America less safe.”

“So, Susan, it's about relationships and the thing that has always been part of the strength of our nation, in addition to our great military, has been that we keep our word,” she added. “But Donald Trump doesn't understand that because he doesn't understand what it means to be honest.”

On the issue of jobs, Harris took aim at the Trump administration trade policy with China.

“You lost that trade war. You lost it. What ended up happening is because of a so-called trade war with China, America lost 300,000 manufacturing jobs,” Harris said. “Farmers have experienced bankruptcy because of it. We are in a manufacturing recession because of it.”

Pence responded by criticizing Joe Biden’s record on China, calling him, “a cheerleader for communist China.”

“When Joe Biden was vice president, we lost 200,000 manufacturing jobs and President Obama said they were never coming back,” Pence said.

PENCE'S CLAIM: "President Trump and I are fighting every day in courthouses to prevent Joe Biden and Kamala Harris from changing the rules and creating this universal mail-in voting that will create a massive opportunity for voter fraud."

FACT CHECK: Pence echoed Trump's attempts to cast doubt on the widespread embrace of vote-by-mail across the country this election by suggesting that universal mail-in voting could lead to massive fraud.

That is historically not true.

Kim Wyman, the Republican secretary of state in Washington -- a state that adopted statewide mail voting in 2011 -- told The New York Times in June that while any voting method could potentially be susceptible to fraud, in her experience as the chief elections official in the state, fraud with mail ballots is low.

"How do you respond to someone that makes an allegation that there's rampant fraud?" she said. "You show them all the security measures that are in place to prevent it and detect it if it does happen."

Ben Ginsberg, a Republican election guru who has spent years looking for voter fraud, wrote in a Washington Post op-ed, "Four decades of dedicated investigation have produced only isolated incidents of election fraud."

"These are painful conclusions for me to reach. Before retiring from law practice last month, I spent 38 years in the GOP's legal trenches. I was part of the 1990s redistricting that ended 40 years of Democratic control and brought 30 years of GOP successes in Congress and state legislatures. I played a central role in the 2000 Florida recount and several dozen Senate, House and state contests," he wrote. "The truth is that after decades of looking for illegal voting, there's no proof of widespread fraud."

Tom Ridge, a Republican who previously served as the governor of Pennsylvania and was the nation's first secretary of Homeland Security, previously told ABC News, "There is absolutely no antecedent, no factual basis for (President Donald Trump's) claim of massive fraud in mail voting."

--ABC News; Kendall Karson