The UN General Assembly approved an Arab-backed resolution calling on Israel to renounce possession of nuclear weapons and put its nuclear facilities under international oversight.
The resolution, adopted in a 161-5 vote on Tuesday, noted that Israel is the only Middle Eastern country that is not party to the Treaty on the Non-Proliferation of Nuclear Weapons.
It called on Israel to "accede to that treaty without further delay, not to develop, produce, test or otherwise acquire nuclear weapons, to renounce possession of nuclear weapons".
The resolution also called on Israel to put its nuclear facilities under the safeguard of the UN's International Atomic Energy Agency.
The United States and Canada were among four countries that joined Israel in opposing the measure, while 18 countries abstained, the Associated Press reported.
Israel is widely considered to possess nuclear arms but declines to confirm it.
General Assembly resolutions are not legally binding but carry moral weight because it is the only body where all 193 UN member states are represented.
The resolution was introduced by Egypt, and includes an Arab-backed effort that failed to gain approval in September at the Vienna-based IAEA.
The UN resolution, titled "The risk of nuclear proliferation in the Middle East," pushed for the establishment of a nuclear weapons-free zone in the Middle East and lamented that US-backed efforts to convene talks were abandoned in 2012.
At the time, Israel criticised Arab countries for undermining dialogue by repeatedly singling out the country in international arenas.
Israel has long argued that a full Palestinian-Israeli peace plan must precede any creation of a Mideast zone free of weapons of mass destruction.
The country also argues that Iran's alleged work on nuclear arms is the real regional threat. Iran denies pursuing such weapons.
US representative Robert Wood, in voting against the resolution at the committee-level last month, said the measure "fails to meet the fundamental tests of fairness and balance. It confines itself to expressions of concern about the activities of a single country."