The 90-minute televised debate will begin at 9pm on Monday (2pm on Tuesday NZ time) at Hofstra University on New York state's Long Island. It is the first of three planned presidential debates.
The tight race for the White House and the unpredictable clash in styles between well-known but polarising opponents has generated wide interest in the potentially pivotal debate, which comes six weeks before the November 8 election after a campaign that has stretched over more than a year.
The gap between the two candidates in recent national opinion polls has narrowed in the past week, with the latest Reuters/Ipsos polling showing Clinton ahead by 4 percentage points, with 41% of likely voters.
Clinton recently pulled ahead of Trump in the crucial battleground state of Florida, according to the Reuters/Ipsos States of the Nation project released on Monday. If the election were held today, Clinton would defeat Trump, with an 88% of reaching the 270 electoral college votes needed, according to the project, which is based on a weekly online tracking poll of more than 15,000 Americans.
The debate will be the first time Clinton and Trump go toe-to-toe and the size of the television-viewing audience is expected to challenge the record of 80 million Americans who watched 1980's encounter between Democratic President Jimmy Carter and Republican Ronald Reagan. Some commentators forecast Super Bowl-sized viewership of about 100 million.
Unlike the single-party debates held during the nominating process, the audience will be asked to remain silent and not applaud or respond to the candidates' answers. The debate will be divided into six 15-minute segments.
Clinton won a coin toss and chose to take the first question. She will have two minutes to answer, after which Trump will be given equal time. Trump will then be given the first question at the beginning of the next segment.
Both Trump and Clinton, who polls show are the least liked White House candidates in modern history, hope to use the debate to erase lingering voter doubts and address campaign-trail weaknesses.
The volatile Trump, a New York businessman and former reality television star, will get a chance to show a depth and steadiness worthy of a commander in chief, while the cautious Clinton will be able to try to connect directly with voters who do not trust her, strategists said.
But Trump, a political newcomer who has often shown more affinity for put-downs than policy, could benefit from lower expectations from voters.
"There is no question it's a lower bar for Trump," said Dan Schnur, a former Republican strategist and now a political scientist at the University of Southern California. "He doesn't have to be brilliant, he just can't be too bombastic."
The stakes are enormous. Clinton once had a sizable lead but that has evaporated amid more questions about her family foundation and use of a private email server while secretary of state under President Barack Obama.
A second Reuters/Ipsos poll released on Monday showed half of America's likely voters would rely on the debates to help them make their choice. More than half, 61%, were hoping for a civil debate and were not interested in the bitterness shown on the campaign trail.
GRUDGE MATCH
Clinton (68) and Trump (70) have regularly exchanged sharp insults, raising the prospect of a fiery grudge match. Trump frequently refers to Clinton as "Crooked Hillary" and has called for her jailing for the email controversy. Clinton condemns Trump as temperamentally unfit for the White House.
Trump dominated the crowded Republican debates with rapid-fire attacks on his rivals but has no experience in a one-on-one debate setting that requires more prolonged discussion of issues.
Clinton has participated in many one-on-one debates on the national stage with Obama during her unsuccessful 2008 presidential campaign and with US Senator Bernie Sanders in their Democratic nominating race earlier this year.
Clinton's camp has done its best to raise the bar for Trump, and in TV interviews on Monday both campaigns tried to frame expectations.
"What we don't want to have is some sort of double standard where Donald Trump can get the most improved award but Hillary Clinton ... is getting judged on the fine points of policy," Clinton campaign manager Robby Mook told NBC News, calling Trump "an entertainer."
Trump campaign manager Kellyanne Conway, separately on NBC, said Clinton's vast experience was unlikely to translate onto the debate stage, where Trump held an advantage. "He's not going to be robotic and scripted," she said.
The role of moderator Lester Holt of NBC News also has come under scrutiny ahead of the debate with the Clinton campaign and her Democratic supporters urging him to correct Trump if he makes false claims.
Trump also has tried to influence Holt and the moderators of the other showdowns with Clinton, saying the candidates should be the ones to correct the record.
But in a year when outsiders like Trump and Sanders have made a mark, Trump's best argument could be that he is a better agent of change than Clinton, said Scott Reed, a veteran Republican operative who is now chief strategist for the US Chamber of Commerce.
Libertarian Gary Johnson and Green Party candidate Jill Stein were not invited to participate in the debate because neither had obtained at least 15% support in national polls, the threshold was established to qualify.
