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: "When President Trump and I took office, America had gone through the slowest economic recovery since the great depression. ... We're going through a pandemic that lost 22 million jobs at the height, we've already added back 11.6 million jobs."

FACT CHECK: With September's jobs report, over 11.4 million jobs have been added since March. But job gains have slowed in the past three months, showing the recovery is starting to lose momentum.

In September, 661,000 jobs were added, which was worse than expectations. The unemployment rate also declined to 7.9%, better than expectations.

The jobs number represented a significant slowdown in the number of jobs added since the economy started opening up after the pandemic induced shutdown.

Airlines such as United and American notified over 30,000 employees that they would be laid off or furloughed because the federal aid expired. Disney, the parent company of ABC News, announced it was eliminating 28,000 theme park jobs in Florida and California, and Cineworld, parent company of Regal Cinemas, the second-largest theater chain in the United States, said Monday that it will close all of its U.S. and U.K. theaters indefinitely, affecting 45,000 employees. These positions weren't included in the September report.

In September, the number of permanent job losses increased by 345,000 to 3.8 million; this measure has risen by 2.5 million since February.

Though the expansion of the U.S. economy was slow under the start of the Obama administration during the Great Recession, in the final four years GDP growth was at a 2.3%, nearly similar to the 2.5% in the first three years of Trump, according to The Associated Press.

--ABC News' Justin Gomez, Layne Winn and Zunaira Zaki