The 90-minute debate wrapped up after the two men traded attacks on abortion, immigration, the wars in Ukraine and Gaza and their handling of the economy as they each sought to shake up what opinion polls show has been a virtually tied race for months.
A hoarse-sounding Biden stumbled over his words on several occasions during the debate's first half-hour, but he found his footing at the halfway mark when he attacked Trump for his conviction for covering up hush money payments to porn star Stormy Daniels, calling him a "felon".
In response, Trump brought up the recent conviction of Biden's son, Hunter, for lying about his drug use to buy a gun.
Joe Biden, 81, at times stumbled over his words while Donald Trump, 78, repeated false statements. (AP PHOTO)
Moments later, Biden noted that almost all of Trump's former cabinet members, including former vice president Mike Pence, have not endorsed his campaign.
"They know him well, they served with him," he said. "Why are they not endorsing him?"
Two White House officials said Biden had a cold. But his uneven performance could deepen voter concerns that the 81-year-old is too old to serve another four-year term.
Trump, meanwhile, unleashed a barrage of criticisms, some of which were well-worn falsehoods he has repeated on the campaign trail, including claims that migrants have carried out a crime wave and Democrats support infanticide.
Asked about the January 6, 2021, attack on the US Capitol by a mob of Trump supporters, the former president refused to accept any responsibility and claimed many of those arrested were innocent.
"This guy has no sense of American democracy," Biden scoffed in response.
Donald Trump refused to accept any responsibility for the January 6 attack on the US Capitol. (AP PHOTO)
Biden also blamed Trump for enabling the elimination of a nationwide right to abortion by appointing conservatives to the US Supreme Court, an issue that has bedevilled Republicans since 2022.
Trump retorted that Biden would not support any limits on abortions and said that returning the issue to the states was the right course of action.
Trump said Biden had failed to secure the southern US border, ushering in scores of criminals.
"I call it Biden migrant crime," he said.
Biden replied, "Once again, he's exaggerating, he's lying."
Studies show immigrants do not commit crimes at a higher rate than native-born Americans.
Each called the other the worst president in history; Biden referred to Trump as a "loser" and a "whiner", while Trump called Biden a "disaster".
At one point, the rivals bickered over their golf games, with Trump bragging about hitting the ball farther than Biden and Biden retorting that Trump would struggle to carry his own bag.
The televised clash on CNN was taking place far earlier than any modern presidential debate, more than four months before the November 5 election.
The two candidates appeared with no live audience, and their microphones automatically cut off when it was not their turn to speak - both atypical rules imposed to avoid the chaos that derailed their first debate in 2020, when Trump interrupted Biden repeatedly.
As the debate began, the two men - who have made little secret of their mutual dislike - did not shake hands or acknowledge one another.
US voters are set to go to the polls in November, with another debate scheduled for September. (AP PHOTO)
The first questions focused on the economy, as polls show Americans are dissatisfied with Biden's performance despite wage growth and low unemployment.
Biden acknowledged that inflation had driven prices substantially higher than at the start of his term but said he deserves credit for putting "things back together again" following the coronavirus pandemic.
Trump asserted that he had overseen "the greatest economy in the history of our country" before the pandemic struck and said he took action to prevent the economic freefall from deepening even further.
Trump took the stage as a felon who still faces a trio of criminal cases, including over his efforts to overturn the 2020 election.
