The debate will hold at Hofstra University on New York state's Long Island.
Democrat Hillary Clinton and Republican Donald Trump will face off for the first time in a presidential debate that could rank as one of the most watched, highly anticipated political showdowns in U.S. history.
The 90-minute debate will begin at 9 p.m. ET tonight (0100 GMT on Tuesday) It's the first of three planned presidential debates.
Here's what you need to know:
1. Clinton will be taking the first question after winning a coin toss. She'll have two minutes to answer after which Trump will be given equal time.
2. Unlike the single-party debates held during the Republican and Democratic nominating campaigns, 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.
3. The candidates are neck and neck as they go toe-to-toe. The gap in national opinion polls has narrowed in the past week, with the latest Reuters/Ipsos polling showing Clinton ahead by 4 percentage points and 41 percent of likely voters.
4. Half of America's likely voters will be relying on the debate to help them make their White House choice, according to a Reuters/Ipsos poll released today.
5. Strategists have said that the volatile Trump, a New York businessman and former reality television star, will get an opportunity to show a 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.