Obama will be one of the opening speakers at the annual meeting of world leaders, which is expected to focus on the civil war in Syria, mounting fears of a strike on Iran and the turmoil sparked by an anti-Islam internet video.
UN leader Ban Ki-moon, France's President Francois Hollande and Qatar's emir, Sheikh Hamad bin Khalifa Al-Thani, a key backer of the Syrian opposition, are also expected to lambast President Bashar al-Assad on the opening morning.
The diplomatic assault will go on all week as Arab and European leaders vent their outrage after UN-Arab League envoy Lakhdar Brahimi warned Monday that the conflict is worsening with no immediate hope of ending the war.
Brahimi also accused Assad of using "medieval" style torture on opponents.
The Islamist occupation of northern Mali, conflict in eastern Democratic Republic of Congo and Somalia's attempts to build a new state out of the ruins of war will also be raised by leaders in New York.
The address will probably be Obama's last major foreign policy speech before the US election on November 6.
Obama will spend only a day in New York – without the normal meetings with world leaders – before heading back to the campaign trail against Mitt Romney.
White House spokesperson Jay Carney insisted, however, that the address was "not a campaign speech".
"This is a speech in which the president will make clear his views, the administration's positions and America's role with regards to a lot of transformation that's happening in the world."
Stung by the deadly anti-US protests sparked by the offensive video, Carney said Obama would reiterate that the United States will "never retreat from the world" and will deliver justice to those who harm Americans.
Obama is also likely to warn Iran that time is running out for a diplomatic exit from the showdown over its nuclear drive and renew his vow that he will use force, if necessary, to stop Iran from building an atomic weapon.
Iran's President Mahmoud Ahmadinejad defiantly warned Monday that his country did not fear a possible Israeli strike on its nuclear installations.
Speaking to CNN, Ahmadinejad sidestepped allegations that Iran is supplying arms to Assad's regime – a longtime ally – and accused other unnamed countries of worsening the conflict by funneling arms to the opposition.
Egypt's newly elected Islamist President Mohamed Morsi meanwhile told US public television's Charlie Rose that he believed Assad should step down but was opposed to any military intervention in the country.
Obama's fleeting visit to the United Nations will not include talks with Israeli Prime Minister Benjamin Netanyahu, with whom he has publicly differed over the Iranian nuclear crisis.
Aides said Obama's compressed election schedule did not allow time for a meeting, sparking Republican criticism, intensified by Obama's comment in an interview on Sunday that Israeli warnings over Iran were "noise."
While the UN assembly is traditionally a forum for a US president to address the world, Obama's speech this year will have a strong domestic undercurrent because of Romney's recent attacks on his foreign policy.
Obama and his rival will also separately address the Clinton Global Initiative, the annual meeting of former president Bill Clinton's humanitarian foundation.
Romney on Monday accused Obama – who had spoken of "bumps in the road" following Arab Spring uprisings – of minimising the murder of four Americans, including US ambassador to Libya Chris Stevens, in Benghazi.
"When the president was speaking about bumps in the road he was talking about the developments in the Middle East, and that includes an assassination," Romney told NBC News.
"It includes a Muslim Brotherhood individual becoming president of Egypt, it includes Syria being in tumult, it includes Iran being on the cusp of having nuclear capability, it includes Pakistan being in commotion."
Polls show Obama is favoured to handle foreign policy, but the Democratic narrative has been complicated by the deadly attack on the US consulate in Benghazi and anti-American protests in a number of Muslim nations. – Sapa-AFP