The UN General Assembly's annual meeting starts on Tuesday, with the focus on talks between Iranian and US officials, and the Syria crisis.
Iran's Foreign Minister Mohammed Javad Zarif will meet diplomats including US Secretary of State John Kerry to discuss Iran's nuclear programme.
It will be the highest level US-Iran meeting for more than 30 years.
Mr Kerry will also seek to iron out differences over Syria with Russian Foreign Minister Sergei Lavrov.
The two men will try to resolve their stances on how to ensure Syria hands over its chemical weapons.
Earlier this month, Russia and the US agreed a deal under the terms of which Syria's chemical weapons arsenal must be eliminated by mid-2014.
However, differences have since emerged over whether the deal should be enforced by a UN resolution under Chapter VII of the organisation's charter, which would authorise sanctions and the use of force.
Open approachThe meeting including Mr Zarif and Mr Kerry is due to take place on the sidelines of the UN General Assembly in New York and will discuss the dispute over Iran's nuclear programme.
- Direct contact between Mr Obama and Mr Rouhani would be first between US and Iranian leaders for 36 years
- Jimmy Carter and Shah Mohammad Reza Pahlavi were last US-Iranian leaders to meet, in 1977
- US Secretary of State Condoleezza Rice and Iranian Foreign Minister Manouchehr Mottaki exchanged "hellos" at Sharm el-Sheikh in 2007 but did not hold talks
Iran insists it is a peaceful programme but Western countries suspect it of trying to develop a nuclear weapon.
The meeting will be attended by foreign ministers from the other four permanent UN Security Council members - Britain, China, France and Russia - and also Germany (the P5+1 group).
It will be the highest level face-to-face contact between the Americans and the Iranians since the 1979 Islamic Revolution.
This in itself is a sign of the potential significance of the opening signalled by the new Iranian President Hassan Rouhani, the BBC's diplomatic correspondent Jonathan Marcus reports.
Mr Rouhani has said he is ready to restart stalled nuclear talks without preconditions. There is speculation that he and US President Barack Obama may shake hands on the sidelines of the UN General Assembly, which would also be a historic first.
The two men recently exchanged letters over the nuclear issue.
Western ministers will want to see an Iranian willingness to make concessions on its nuclear programme if there is to be any lifting or lightening of UN and Western sanctions, our correspondent reports.
Iran for its part will want a clear indication that the US is willing to treat Iran with the respect it believes it deserves as a significant regional player, he adds.
The EU's foreign policy representative, Baroness Ashton, met Mr Zarif on Monday and described their discussion as "good and constructive." She said her team would hold talks with Mr Zarif again in October in Geneva to assess progress.
Last week, Mr Rouhani said that his country would never build nuclear weapons.
In his election campaign earlier this year, Mr Rouhani pledged a more moderate and open approach in international affairs.
Meanwhile, Brazilian President Dilma Rousseff is to be the first world leader to address the General Assembly, and is expected to refer to a row between Brazil and the US following leaks about Washington's cyber-spying operations.
The US National Security Agency (NSA) is alleged to have targeted Ms Rousseff's emails and phone calls as well as carrying out widespread surveillance of other Brazilian citizens.
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