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.

Page pivoted the conversation to climate change, noting the U.S. has seen record-setting hurricanes in the South and record-setting wildfires in the West this year, setting the stakes and posing the first question to the vice president.

"Do you believe, as the scientific community has concluded, that man-made climate change has made wildfires hotter and more deadly and hurricanes wetter and more damaging?" Page asked.

Pence didn't directly answer but warned Harris would sign the U.S. back into the Paris Climate Accord and falsely claimed Biden and Harris have committed to abolishing fossil fuel and banning fracking.

"President Trump and I believe that the progress that we have made in a cleaner environment has been happening precisely because we have a strong free market economy," Pence said.

Harris, once a proponent of the Green New Deal as both a co-sponsor of Sen. Bernie Sanders' bill and as a presidential candidate -- is now embracing Biden's climate plan and defended her running mate's record.

"First of all, I will repeat, and the American people know, that Joe Biden will not ban fracking. That is a fact. That is a fact," Harris began. "We have seen a pattern with this administration, which is, they don't believe in science."

"Joe sees what's happening on the Gulf states, which are being battered by storms. Joe has seen and talked with the farmers in Iowa whose entire crops have been destroyed because of floods. And so Joe believes, again, in science," Harris said, adding that a Biden-Harris administration would "re-enter the climate agreement with pride."

Page then asked if Pence agrees with Harris that climate change poses an existential threat to humans.

"As I said, Susan, the climate is changing. We'll follow the science," Pence said, before launching into an attack on Biden's tax plan.