The event, which is expected to be watched – and parsed – by tens of millions of Americans, could draw a record number of viewers when it kicks off at 9:00 pm (0100 GMT Tuesday).
Many Americans are uncertain what to expect from the clash, which pits two vastly different candidates against each other on one tiny stage.
Clinton, 68, enters the fray as a polished former secretary of state, who after almost 40 years of public service is very well versed on the issues.
Trump, a 70-year-old billionaire and former reality TV star, is good on his feet, and unpredictable – more comfortable in the limelight than on issues.
As many as 90 million people are expected to tune in as the pair face off at Hofstra University in New York six weeks before the November 8 election.
The debate is being held one day after a Washington Post-ABC News poll revealed that Clinton’s slim advantage over Trump from last month has evaporated.
She is tied with Trump at 41 per cent among registered voters, with Libertarian candidate Gary Johnson at seven per cent and Green Party candidate Jill Stein at two per cent , according to the poll.
In a two-way match-up, Trump and Clinton were even at 46 per cent of registered voters. The survey showed a statistical tie among likely voters as well.
Many analysts say debates usually don’t win candidates the election but can well lose it for them. A single sentence or the slightest slip can do serious damage.
“I think this thing will be close right up until the end,” said Clinton running mate Tim Kaine. “We have to make our case every day. The debates are a great way to do that.
Unfair to be ‘traffic cop’
The Clinton campaign, which hopes its candidate becomes the first female president in US history, expressed concern Sunday over a double standard, with a number of experts saying the bar has been raised higher for Clinton.
“It’s unfair to ask that Hillary Clinton both play traffic cop with Trump, make sure that his lies are corrected, and also to present her vision for what she wants to do for the American people,” Clinton campaign manager Robbie Mook told broadcaster ABC.
The Clinton team is concerned that the moderator, Lester Holt of NBC, will toss simpler “softball” questions in Trump’s direction while pressing Clinton with a much more challenging interrogation.
“All that we’re asking is that if Donald Trump lies, that it’s pointed out,” Mook said.
But Trump has already stated that he does not believe Holt’s purpose as moderator is to police each candidate.
Debate mind games were also on display as Trump threatened to invite Gennifer Flowers, a former lover of Bill Clinton, to watch the high-stakes battle from a front-row seat.
Trump campaign manager Kellyanne Conway said it was meant to show the New York billionaire had ways “to get inside the head of Hillary Clinton” but she told CNN there were no plans to actually invite Flowers.
Nine per cent of voters by some estimates still don’t know who to cast their ballot for, after a long campaign in which bitter attacks have often replaced talk of substance.
And this year has been like none in the past, with Trump using social media around the clock in combative fashion, while often making mistakes, misstatements and blunders that do not seem to trouble his base.
Preparation ‘going very well’
Ahead of the debates Clinton has been cloistered with aides and her papers at home in Chappaqua, north of New York, even practicing with relatives playing Trump.
She has been focusing on his psychological profile, with a goal to get Trump to crack, to show that he can’t control himself and lacks the even-handed temperament a president needs.
If he reacts by attacking, Trump risks losing votes from women; he already has a harder time with women voters, and they make up 53 per cent of those who turn out.
Trump in turn says his debate practice is “going very well,” trying to at least appear relaxed. Amid preparations, he has continued with campaign rallies, including Saturday night in Roanoke, Virginia.
On Sunday both candidates met with Israeli Prime Minister Benjamin Netanyahu. Trump later issued a statement pledging to rrecogniseJerusalem as Israel’s “undivided capital” if elected.
Clinton, making her second presidential bid, is an old hand at debates and considered solid – so in some ways, she may have more to lose.
Some 88 per cent of Americans say they believe she is smart, but in the latest poll 66 per cent said they do not find her honest.
In addition, Clinton’s image has been sullied by Trump attacks over her email scandal, the Clinton Foundation’s alleged pay-to-play donations, and her ties to Wall Street.
Some 57 per cent have a negative opinion of Clinton who they see as cerebral, distant or cold. Trump’s negative numbers are virtually identical.