The U.N. declaration recognizes rights of indigenous groups, like American Indians, in such areas as culture, property and self-determination.
"I want to be clear: what matters far more than words, what matters far more than any resolution or declaration, are actions to match those words," Obama said as he announced U.S. support for the declaration in opening the White House Tribal Nations Conference at the Interior Department.
The United States had been one of a handful of nations to hold back from endorsing the declaration in the past.
Welcoming the move, Robert Coulter of the Indian Law Resource Center said in a written statement: "The Declaration sets an agenda for the United States and Indian nations to design a reasonable approach to a progressive realization of the duties and responsibilities in it."
"It serves as a guide for consultations among Indian and Alaska Native nations and U.S. governmental departments and agencies," he said.
Obama told the conference gathering of some 500, including more than 320 representatives of federally recognized tribes, that the White House would issue further details about the endorsement of the declaration later.
Critics say the declaration could lead to American tribes gaining more independence and economic power than is reasonable.
Recalling a presidential campaign visit he paid to the Crow Nation reservation in Montana, he said the Crow name he was given was: "One who helps people throughout the land."
He joked that his wife said his name should be: "One who is not picking up his shoes and his socks."
Fawn Sharp of the Quinault India Nation said in introducing Obama that "extraordinary strides have been made in restoring trust between" Indian country and the federal government under his administration.