The state visit, by far the most high-profile and consequential of Charles's reign, marks the 250th anniversary of the US declaration of independence from British rule, and is the first to the country by a British monarch for two decades.
It begins with a private meeting with self-proclaimed royal fan President Donald Trump, and includes an address to Congress and a lavish dinner at the White House.
But the long-planned trip has become enmeshed in the political spat between the two countries over the US-Israeli war on Iran, which led Trump to voice deep displeasure with the British government for failing to support the offensive.
The shooting on Saturday at the White House Correspondents' Association dinner in Washington, with the president and officials in his administration the likely targets according to the US acting attorney general, has cast a further pall over the visit.
Buckingham Palace said the trip would still go ahead as planned following discussions between British and US authorities to determine if the incident would affect the royals' plans.
"The King and Queen are most grateful to all those who have worked at pace to ensure this remains the case and are looking forward to the visit getting under way tomorrow," a palace spokesperson said on Sunday.
On arriving in Washington, the King and Queen have a private tea with the president - an unabashed lover of the British royal family who regularly describes Charles as a "great man" - and his wife, first lady Melania Trump.
The 77-year-old King, who is still undergoing treatment for cancer, will address Congress the next day - just the second time a British monarch has done so.
The royals will then head to New York where they will commemorate those killed in the September 11, 2001, attacks before the 25th anniversary, while the Queen will also mark the centenary of children's stories featuring Winnie the Pooh.
The US trip concludes in Virginia with the King meeting those involved in conservation work, a nod to his half century of environmental campaigning.
The government of British Prime Minister Keir Starmer hopes the visit will shore up the future of the two allies' "special relationship", which is at its lowest point since the Suez Crisis in 1956.
While Trump has eased his criticism of Britain in recent days over its response to the Iran war, an internal Pentagon email has set out how the US could review its position on Britain's claim to the Falkland Islands as punishment for its lack of support, once again straining ties.
One issue off the table during the visit is the Jeffrey Epstein scandal, with royal sources saying it is not possible for the royal couple to meet any victims of Epstein during the tour, as some have requested, to avoid affecting any potential criminal cases.
Charles' brother, Andrew Mountbatten-Windsor, whose reputation and royal standing has been destroyed over his links to the late US sex offender, is faces police inquiries over his connections.
The former Prince Andrew has denied any wrongdoing.
