The Republican candidate turned up in trademark form, launching broad attacks on his opponent, claiming she did not have “the look” or “stamina” to be President.
Fact-checkers have been analysing claims made by both sides during the 90 minutes debate, with several of Mr Trump’s statements criticised as “nonsensical” by opponents.
When asked how he felt about Barack Obama’s consideration of whether the US should scrap its policy of using nuclear weapons first in any prospective conflict, Mr Trump appeared to do several U-turns.
Firstly, he appeared to support nuclear disarmament, saying: “I would like everybody to end it, just get rid of it. But I would certainly not do first strike... I think that once the nuclear alternative happens, it’s over.”
Mr Trump said: “China should go into North Korea. China is totally powerful as it relates to North Korea.
“And by the way, another one powerful is the worst deal I think I’ve ever seen negotiated that you started is the Iran deal. Iran is one of their biggest trading partners. Iran has power over North Korea.
“And when they made that horrible deal with Iran, they should have included the fact that they do something with respect to North Korea. And they should have done something with respect to Yemen and all these other places.”
Mr Trump went on to claim the deal struck with Iran over its weapons capability would “lead to nuclear problems”.
He garnered further criticism for claiming Ms Clinton has been trying to “fight Isis” for 50 years – decades before the group’s existence.
Ms Clinton had been outlining her policies to tackle the militant group, which controls swathes of Syria, Iraq and Libya and has affiliates launching terror attacks around the world, when her rival interrupted.
“You’re telling the enemy everything you want to do,” Mr Trump said. “No wonder you’ve been fighting Isis your entire adult life.”
The Republican candidate appeared stunned by the claim, which triggered a ripple of gasps and laughter in the audience.
“That’s a…that’s…please go to the fact-checkers and get to work,” Ms Clinton said.
Born in 1947, the Democrat candidate is 68 years old and became a legal adult when she turned 18 in 1965.
Isis evolved from a jihadist group established in Iraq by Abu Musab al-Zarqawi in 1999, which was initially known as Jama'at al-Tawhid wal-Jihad, before changing to al-Qaeda in Iraq (AQI) after pledging allegiance to Osama bin Laden’s network in October 2004.
The group operated under numerous guises until leaders declared it the Islamic State in Iraq (ISI) in 2006, adding the “and al-Sham [Syria]” to make “Isis” in 2013 after fighters were sent to join the Syrian civil war.
But an internal power struggle between “caliph” Abu Bakr al-Baghdadi and heads of the Syrian arm known as Jabhat al-Nusra caused al-Qaeda to cut ties with Isis in early 2014, shortly before the terrorist group launched its lightning advance across Iraq and Syria.
Mr Trump’s business career has long been a bone of contention, with him citing it as one of his main qualifications for becoming President and touting his skill at “making a good deal”.
Opponents, meanwhile, have cited controversies including a discrimination lawsuit brought by black tenants in the 1970s and Mr Trump’s activity during the US’ disastrous subprime mortgage crisis.
Mrs Clinton called the ensuing recession “a perfect storm” of bad tax policy and mismanagement.
“Donald was one of the people who rooted for the housing crisis,” she continued.
“He said, back in 2006, 'Gee, I hope it does collapse, because then I can go in and buy some and make some money.' Well, it did collapse.”
Mr Trump did not refute the allegation, responding: “That's called business, by the way.” He provided no further explanation.
Blaming Hillary Clinton ‘for everything’
Asked to defend his proposal to cut taxes for the rich, Mr Trump unleashed a stream of consciousness ending with the accusation: “We have no leadership. And honestly, that starts with Secretary Clinton.”
She responded: “I have a feeling that by, the end of this evening, I'm going to be blamed for everything that's ever happened.”
“Why not?” Mr Trump shrugged.
Ms Clinton laughed before added: “Yeah, why not, you know, just join the debate by saying more crazy things?”
Earlier in the debate, he addressed his adversary as “Secretary Clinton” before asking; “Is that okay? I want you to be very happy. It's very important to me.”
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