The United States is the world's largest exporter of conventional arms. The treaty would set up greater international guidelines to prevent the export to conflict areas and extremists.
Secretary of State John Kerry, signing on behalf of the United States in an oversized book at the UN headquarters, called the treaty a "significant step" for global peace efforts.
"This is about keeping weapons out of the hands of terrorists and rogue actors," Kerry said after signing the Arms Trade Treaty in front of UN officials.
Kerry devoted much of his comments to assuaging concerns inside the United States, where the weapons industry holds significant political sway.
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The treaty requires ratification from the Senate and some senators have already voiced concern about the treaty, which has energized US conservatives who are deeply suspicious of both gun regulations and the United Nations.
"This treaty will not diminish anyone's freedom," he said.
"In fact, the treaty recognizes the freedom of both individuals and states to obtain, possess and use arms for legitimate purposes," he said.
The United States hesitated at finalizing the arms treaty as Obama faced re-election last year.
But the United States was part of efforts that sealed the treaty earlier this year, with only three nations -- Iran, North Korea and Syria -- in opposition.
Advocates for the treaty said that they expected more than 100 countries to sign it by the end of today, which comes during the annual UN General Assembly summit.