Najib, who was accompanied by his wife Datin Seri Rosmah Mansor, left by a special aircraft at 5.30pm from the KL International Airport.
Deputy Prime Minister Tan Sri Muhyiddin Yassin and his wife Puan Sri Noorainee Abdul Rahman and Inspector-General of Police Tan Sri Ismail Omar were among those who were at the airport to send off Najib and Rosmah.
Najib is scheduled to deliver a speech at the general debate session of the general assembly on Monday.
The 65th session carries the theme ‘Reaffirming the Central Role of the United Nations in Global Governance’.
The prime minister is also scheduled to attend the Second Asean-United States Leaders’ Meeting tomorrow in New York to be chaired jointly by President Nguyen Minh Triet of Vietnam, who is the Asean chairman, and US President Barack Obama.
Najib will also attend bilateral meetings with his counterparts.
He is also scheduled to host an Aidilfitri open house for the Malaysian students and community in New York on Saturday.
The prime minister and his wife are scheduled to return to Malaysia on Sept 30.