Hollywood actor Leonardo DiCaprio, former US vice president turned advocate Al Gore, UN Secretary General Ban Ki-moon and New York Mayor Bill de Blasio are due to take part in the "People's Climate March."
The event has been endorsed by more than 1,400 organizations, including environment, faith and justice groups, as well as labor unions. Students have mobilized marchers at more than 300 college campuses.
The protest will wind its way through Midtown Manhattan on a two-mile (3.2-kilometer) route starting at 11:30 am (1530 GMT).
Artists have been making props ahead of the protest, working on floats in the hipster artist neighborhood of Bushwick in Brooklyn.
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Around the world, more than 2,700 climate events in 158 countries are planned to coincide with the New York march, including rallies in New Delhi, Jakarta, London, Melbourne and Rio de Janeiro.
The rallies will take place ahead of a climate change summit hosted by Ban Tuesday on the sidelines of the United Nations General Assembly.
More than 120 heads of state and almost 40 ministers are due to attend the summit that Ban hopes will energize negotiations on reaching a deal on cutting greenhouse gas emissions.
The meeting will set the stage for a crucial conference in Paris in December 2015 aimed at finalizing an agreement.
"We are breaking ground here on many different levels," UN climate chief Christiana Figueres told reporters.
"First, we're going to see unprecedented public mobilization for climate action.