Hosted by ABC News, the event takes place on Tuesday evening in Philadelphia and the world is expected to tune in to see who comes out on top.
It will be the second presidential debate of the 2024 election but the first between the two candidates, who have yet to meet each other. After lengthy negotiations, the candidates have agreed to a strict set of rules to try to make it a fair debate.
They have agreed to abide by the terms set out by Mr Trump and President Joe Biden used during the first debate in June 27, which included muted microphones, no pre-written notes, no live audience, no sitting and no speaking with campaign staff during commercial breaks.
Republican candidate Donald Trump is expected to target the Democratic candidate, Kamala Harris, over immigration and the cost of living.
Ms Harris is likely to fire back at Mr Trump’s record while in office, his controversies and his culpability in the Capitol riots in January 2021.
Here is how you can watch in the UK.
Hosted by ABC News, the event starts on Tuesday, September 10 at 9pm EDT, which is 2am in the UK, and takes place at the National Constitution Center in Philadelphia.
Channel 4 is the only UK broadcaster showing the debate live but it will be streamed on other platforms.
The event is being hosted by ABC but will be on other US networks, including C-Span, PBS, MSNBC and Fox News, and streamed online via ABC’s website, and YouTube channel and via Disney+ and Hulu.
Who is heading the coverage for ABC News’s debate?
The showdown will be overseen by ABC anchors David Muir and Linsey Davis. They have said they will not share the questions or topics up for discussion with the candidates beforehand.