Republican Vice President Mike Pence and Democratic challenger Kamala Harris squared off in Utah, ahead of the 3 November election.
Here are some of the key quotes from the debate, which was moderated by USA Today journalist Susan Page:
The coronavirus pandemic
Harris: "The American people have witnessed what is the greatest failure of any presidential administration in the history of our country: 210,000 dead people in our country forjust the last several months."
Pence: "I want the American people to know that from the very first day President Donald Trump has put the health of America first."
Harris: "On January 28, the vice president and the president were informed about the nature of this pandemic. They were informed that it's lethal ... And they knew what was happening and they didn't tell you."
Pence: "The reality is when you look at the Biden plan (to fight the pandemic), it reads an awful lot like what President Trump and I and our task force have been doing every step of the way ... it looks a little bit like plagiarism."
Harris on a Covid-19 vaccine: "If the public health professionals, if Dr Fauci, if the doctors tell us that we should take it, I'll be the first in line to take it absolutely, but if Donald Trump tells us to take it, I'm not taking it."
Pence: "The fact that you continue to undermine public confidence in a vaccine - if the vaccine emerges during the Trump administration - I think is unconscionable ... stop playing politics with people's lives."
Harris: "Joe Biden believes you measure the health and the strength of America's economy based on the health and the strength of the American worker and the American family. On the other hand, you have Donald Trump, who measures the strength of the economy based on how rich people are doing, which is why they passed a tax bill benefiting the top 1% ... that the American people will now have to pay for."
Pence: "More taxes, more regulation, banning fracking, abolishing fossil fuel, crushing American energy and economic surrender to China is a prescription for economic decline. President Trump and I will keep America growing. The V-shaped recovery that's under way right now will continue with four more years of President Donald Trump."
Harris: "If you have a pre-existing condition, heart disease, diabetes, breast cancer, they're coming for you. If you love someone who has a pre-existing condition they are coming for you."
Pence: "Obamacare was a disaster. The American people remember well. President Trump and I have a plan to improve healthcare and to protect pre-existing conditions for every American."
Pence: "On Day One, Joe Biden's going to raise your taxes."
Harris: "Joe Biden has been very clear: he will not raise taxes on anybody that who makes less than $400,000 a year."
The Supreme Court
Pence: "If you haven't figured it out yet, the straight answer is they (the Democrats) are going to pack the Supreme Court, if they somehow win this election."
Harris: "Do you know that of the 50 people who President Trump appointed to the court of appeals for lifetime appointments, not one is black? This is what they've been doing. You want to talk about packing a court, let's have that discussion."
Harris: "You've got to know who your adversaries are, and keep them in check. But what we have seen with Donald Trump is that he has betrayed our friends and embraced dictators around the world. Let's take for example, Russia."
Pence: "When President Trump came in ... ISIS had captured an area of the Middle East the size of Pennsylvania. President Trump unleashed the American military and our armed forces destroyed the ISIS caliphate."
Pence: "Now with regard to climate change, the climate is changing. But the issue is, what's the cause? And what do we do about it? President Trump has made it clear that we're going to continue to listen to the science."
Harris: "Let's talk about who is prepared to lead our country over the course of the next four years on what is an existential threat to us as human beings. Joe is about saying we're going to invest in renewable energy ... we will achieve net zero emissions by 2050, (be) carbon neutral by 2035 ... We will also re-enter the climate agreement with pride."
Harris: "What ended up happening is because of a so-called trade war with China, America lost 300,000 manufacturing jobs. Farmers have experienced bankruptcy because of it. We are in a manufacturing recession because of it."
Pence response: "Look, lost the trade war with China? Joe Biden never fought it. Joe Biden's been a cheerleader for communist China over the last several decades."
The US military
Harris: "This is about a pattern of Donald Trump's, where he has referred to our men who are serving in our military as 'suckers' and 'losers'. Donald Trump, who went to Arlington Cemetery, and stood above the graves of our fallen heroes and said, what's in it for them."
Pence: "President Donald Trump not only respects but reveres all of those who served in our armed forces, and any suggestion otherwise is ridiculous."