David Cameron is to become the first sitting British Prime Minister to be on David Letterman's Late Show in New York.
The appearance, due to happen on Wednesday, is part of a visit to Manhattan for the 67th UN General Assembly.
The Prime Minister will use the chat show to "seize on the Olympic legacy" and promote the UK to American tourists and businesses, according to Downing Street.
Letterman's popular programme reaches around three million viewers per night and recently hosted US President Barack Obama.
Tony Blair appeared on it twice after he left office and Boris Johnson has also sat in the host's hot seat.
But Mr Cameron lands in New York today with more than chat shows on his agenda.
His visit comes amid ongoing concern over the violence in Syria.
New UN envoy to Syria Lakhdar Brahimi offered a down-beat assessment of the country in a briefing to the Security Council on Monday.
He said: "Unfortunately, it is a very grim situation.
"There is no disagreement anywhere that the situation is bad and getting worse. It is a threat to the region and to the peace and security in the world."
Foreign Secretary William Hague said the UK would use the summit to convince more countries to spend cash and time trying to solve what the UN has described as a worsening humanitarian crisis.
The Prime Minister will also meet a number of world leaders and co-chair a panel on the UN's Millennium Development Goals - targets to eradicate extreme poverty by 2015 - before addressing the 193-member assembly later in the week.
Mr Obama is due to give his speech to the UN General Assembly later.
He is expected to address the ongoing protests in parts of the Arab world over a crude US-made anti-Islam film, as well as escalating tensions over Iran.