Boris Johnson has touched down in New York, where he will discuss Brexit with Angela Merkel, Emmanuel Macron, Leo Varadkar and Donald Tusk.
Climate change and tension in the Middle East will also be high on the agenda, as the Prime Minister attends the United Nations General Assembly, where he will also meet US President Donald Trump.
RAF Voyager landed in New York on Sunday evening – the early hours of Monday UK time – carrying with it Mr Johnson and assorted members of the media.
With the PM staying in the US until Wednesday, he could be out of the UK when the Supreme Court announces its decision on the legality of his prorogation of Parliament as Brexit beckons.
The UN is holding its Climate Action Summit, and Mr Johnson is set to announce environmental policies over two speeches.
Scientists will be able to use up to £1 billion of the aid budget inventing new technology to tackle the climate crisis in developing countries, under a clean energy fund named in honour of British physicist and suffragette Hertha Ayrton.
A further £220 million from the overseas aid budget will be used in efforts to save endangered species from extinction in an international biodiversity fund.
But brokering a new EU departure deal will be high on the PM’s list of priorities, with the October 31 deadline looming.
He is expected to talk about Brexit and the attacks on the Aramco oil facilities in Saudi Arabia in a meeting with French President Mr Macron and German Chancellor Mrs Merkel on Monday.
That will follow talks with European Council president Mr Tusk, who will have already met Mr Macron and Mrs Merkel.
He will go on to meet his Irish counterpart Leo Varadkar and Mr Trump separately on Tuesday.
Mr Varadkar’s deputy, Simon Coveney, has said a “wide gap” remains between Mr Johnson and the EU in seeking a fresh deal.
With Mr Trump, the PM is expected to discuss Iran, Afghanistan and the climate crisis – a thorny subject for the president, who has described it as a “hoax”.
The PM’s partner, Carrie Symonds, is also expected to attend the General Assembly.
But a senior Government official stressed she was travelling for her own work with environmental group Oceana and not with the PM.
Other bilateral meetings anticipated for the PM are with Turkey’s President Recep Tayyip Erdogan, Indian PM Narendra Modi, Egypt’s President Abdel Fattah el-Sisi, Ukraine’s President Volodymyr Zelensky, Jordan’s King Abdullah II and UN Secretary-General Antonio Guterres.