Only Israel joined the United States in opposing the measure, which was backed by 186 countries.
This marks the 20th consecutive year in which the General Assembly has called on Washington to abandon the sanctions against the Communist-ruled island.
Shortly before the voting, Cuba's foreign minister noted the "categorical and overwhelming" support of the international community against the embargo, and said that the U.S. government has projected "a false image of flexibility" on the issue by easing some restrictions on travel and remittances to the island.
"The blockade and the sanctions remain intact, fully applied and in recent years its extraterritorial character has been accentuated," Bruno Rodriguez said.
He said that under President Barack Obama "the persecution of Cuban financial transactions" has been stepped up "all over the world, without respecting the laws of third-party countries nor the opposition of their governments."
For his part, the U.S. ambassador at the debate, Ambassador Ronald Godard, said that the embargo is a bilateral affair and "not appropriately a concern of this assembly."
The U.S. diplomat said the "overarching goal" of Washington's policy toward Havana "is to encourage a more open environment in Cuba and increased respect for human rights and fundamental freedoms."
The embargo has cost his country $975 billion since its imposition in 1962, Rodriguez said Tuesday.
The embargo officially began on Feb. 7, 1962, during the administration of President John F. Kennedy, though Washington began implementing various sanctions within months of Cuba's January 1959 revolution.