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.

Opening the night's discussion on the economy, Harris said firmly that Biden would repeal Trump's 2017 tax cuts "on day one."

"He'll get rid of it," she said. "And what he'll do with the money is invest it in the American people and through a plan that is about investing in infrastructure, something that Donald Trump said he would do, I remember hearing about some infrastructure week, I don't think it ever happened."

"But Joe Biden will do that. He'll invest in infrastructure. It's about upgrading our roads and bridges but also investing in clean energy and renewable energy," she added.

Pence responded by attacking the state of the economy after the Obama administration and tried to tie Biden and Harris to the Green New Deal proposal.

"When President Trump and I took office, America had gone through the slowest economic recovery since the Great Depression," he said. "Because when Joe Biden was president, they tried to tax and spend and regulate and bail our way back to a growing economy."

When Harris responded again during the open discussion section, she underscored that her and Biden's plan would only raise taxes on wealthy Americans.

"We saw enough of it in last week's debate, but I think this is supposed to be a debate based on fact and truth," she said.  "And the truth and the fact is, Joe Biden has been very clear, he will not raise taxes on anybody who makes less than $400,000."

Pence argued that the Trump tax plan lowered taxes for average Americans and that a repeal would mean higher taxes for everyone, not just the wealthy.

"It would be important if you said the truth. Joe Biden said twice in the debate last week that he's going to repeal the Trump tax cuts," he said. "That was tax cuts that gave the average working family $2,000 in a tax break every single year."