Mr Trump takes the podium at the General Assembly just after Brazil's Michel Temer, presenting his message to the world as he pushes his nationalist "America First" agenda.
At a first UN appearance on Monday, Trump vowed to push for reform at the world body that he once disparaged as a "club" where "people get together, talk and have a good time."
Today, the US leader will outline his foreign policy priorities, from confronting North Korea over its nuclear and missile tests to deciding the fate of the Iran nuclear deal.
A top White House aide said Trump will take aim at "rogue regimes that threaten world stability and peace," singling out Pyongyang and Tehran during his 30-minute remarks and urging responsible nations to step in to curb their behavior.
French President Emmanuel Macron, seen as the face of a more confident post-Brexit Europe, will also be making his first address to the 193-nation assembly.
His speech will likely offer a sharp contrast to Trump's world view.
The French leader has embraced multilateralism and even went so far as to turn Trump's "Make America Great Again" slogan into a motto in favor of climate protections: "Make the Planet Great Again."
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