The stakes could not be higher: the first woman to win the White House nomination for a major US party, against a New York tycoon turned reality star who has upended the political establishment.
Commentators call it a clash of the titans: a 90-minute test of endurance between Clinton the Democrat, arguably the most experienced US presidential candidate in history, against Trump the Republican, perhaps the least experienced White House nominee for a major party.
The outcome could shape the last six-week stint of an election that has deeply polarized the country and left Trump fighting to overcome allegations of bigotry and sexism.
Time and place
Monday at 9:00 pm (11.00am AEST), at Hofstra University in the city of Hempstead on Long Island, an hour's drive from New York. Hofstra is no newcomer to presidential debates, having hosted them in 2008 and 2012.
Length and format
Ninety minutes, in six 15-minute segments with no commercial interruptions. Questions will focus on three broad themes: "America's Direction," "Achieving Prosperity" and "Securing America."
The two candidates will be alone on the stage, each standing behind a lectern.
The moderator will open each segment with a question. Each candidate will have two minutes to respond; each will then be allowed to reply to the other's response. The moderator will use the remaining time for follow-up questions.
Each broad theme will be discussed for 30 minutes.
Moderator
Lester Holt, 57, the respected anchor of NBC's evening news program, the country's most widely watched. He moderated one of the Democratic primary debates in January.
The stakes for Hillary Clinton
The bar is higher for the Democratic candidate, given her experience and detailed knowledge of the issues. Clinton will have to show that she is presidential but also honest (66 percent of Americans do not think so), while proving that she has fully recovered from her recent bout of pneumonia. Clinton is not particularly well-liked, and anything she can do to create an emotional bond with voters could boost her cause.
The stakes for Donald Trump
Trump needs to convince voters that he has what it takes to be president, that he has at least an adequate familiarity with the issues and can make it through a high-pressure debate against a single opponent without losing his self-control. He also needs to reassure Republicans that although he is in many ways an outsider, he would serve as a Republican president.
A new audience record?
The current record for a televised presidential debate is 80.6 million viewers, set by the 1980 encounter between the Democratic incumbent, Jimmy Carter, and his Republican challenger, former California governor Ronald Reagan. Many analysts expect that to be broken on Monday.
Third-party candidates
Gary Johnson, the Libertarian candidate, and Jill Stein, the Green Party nominee, were not invited to the debate. They did not reach the threshold, set by the Commission on Presidential Debates, of an average 15 percent support based on five national opinion polls.
Johnson's support is currently at 7.2 percent and Stein's at 2.3 percent.
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Next debates
October 9 and 19, at St Louis, Missouri, and Las Vegas, Nevada.
Polls tied, stocks tumble
Stocks skidded on Wall Street Monday with the Dow Jones Industrial Average dropping 0.9 percent to 18,094.83 amid unease over the outcome of Monday's debate.
"The market is beginning to realize that it may not be an easy win for Clinton," said Peter Cardillo, chief economist at First Standard Financial. "Normally a Republican win would be positive for the stock market, but with Trump it may create a lot of uncertainties."
The latest opinion polls have Clinton and Trump virtually tied: 41 percent each according to the Washington Post-ABC poll and 43 for Clinton to Trump's 42 percent according to Quinnipiac University.
The Quinnipiac poll found that voters expect Clinton to win the debate 41 to 32 percent, and that 84 percent said they intend to watch.
The Clinton campaign has expressed concern of being held to a double standard, saying the bar is higher for her while Trump stood to win praise for a merely adequate performance.
"All that we're asking is that if Donald Trump lies, that it's pointed out," Clinton campaign manager Robbie Mook told ABC.
Trump has already stated that he does not believe Holt's role as moderator is to police each candidate.
He also previously accused Holt -- a registered Republican -- of being a Democrat.
According to the Washington Post/ABC News poll, both Clinton and Trump are viewed unfavorably by 57 percent of registered voters.
While voters find both candidates lacking in honesty, Clinton's ratings were worse, with just 33 percent of voters finding her honest and trustworthy and 66 percent saying she is not.
