The US Senate never ratified the 2013 Arms Trade Treaty after former president Barack Obama endorsed it. Trump said he was revoking his predecessor's signature.
"We will never surrender American sovereignty to anyone," Trump said in a speech to the National Rifle Association in Indianapolis.
"We will never allow foreign bureaucrats to trample on your Second Amendment freedom," he said, referring to the constitutional right to bear arms.
"And that is why my administration will never ratify the UN arms trade treaty."
"I am officially announcing today that the United States will be revoking the effect of America's signature from this badly misguided treatment (sic). We're taking our signature back."
The treaty, which entered into effect in December 2014, seeks to regulate the flow of weapons into conflict zones.
It requires member countries to keep records of international transfers of weapons and to prohibit cross-border shipments that could be used in human rights violations or attacks on civilians.
While 130 countries originally signed the treaty, only 101 have ratified and joined it. Those include major powers like France, Germany and the United Kingdom.
UN praises landmark achievement
The world's largest arms traders, the United States, China and Russia, have not joined.
Asked about Trump's announcement, the United Nations praised the arms trade treaty as a "landmark achievement" in efforts to ensure responsibility in international arms transfers.
UN spokesman Stephane Dujarric said the ATT is "the only global instrument aimed at improving transparency and accountability in the international arms trade."
He said the treaty was "particularly important in present times, when we witness growing international tensions and renewed interest in expanding and modernising arsenals."
In a statement the White House said the treaty "fails to truly address the problem of irresponsible arms transfers, while providing a platform for those who would seek to constrain our ability to sell arms to our allies and partners."
It also claimed that some groups are trying to use the treaty to overturn "sovereign national decisions" on arms exports - pointing to one effort to block the British government's sale of weapons to Saudi Arabia.
"The ATT is simply not needed for the United States to engage in responsible arms trade," the White House said.
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