The final tally Tuesday was 188-3, with Israel and Palau joining the United States. The Marshall Islands and Micronesia both abstained. Last year's tally for the symbolic measure was almost identical, 186-2, with three abstentions.
The embargo was first enacted in 1960 following Cuba's nationalization of properties belonging to U.S. citizens and corporations. Sanctions against the Caribbean nation were further strengthened to a near-total embargo in 1962.
Speaking before the General Assembly, Cuban Foreign Minister Bruno Rodriguez railed against the embargo calling the U.S. policy "inhumane, failed and anachronistic."
"Keeping this policy in force is not in the national interest of the United States. Quite on the contrary, it harms the interests of its citizens and companies — especially in times of economic crisis and high unemployment — which, according to every poll, are demanding a change of policy," Rodriguez said. "What's the point of encroaching on the constitutional and civil rights and the freedom of travel of Americans by preventing them from visiting the Island when they can visit any other place in the planet, including those where their country is waging wars?"
Rodriguez added that although U.S. President Barack Obama had offered a new beginning with Cuba, after the 2008 election, "the reality of the last four years has been characterized by a persistent tightening of the economic, commercial and financial blockade."
The United States has made clear that although some restrictions on travel and remittances have been eased under the Obama administration it is not prepared to lift the sanctions entirely until the communist-run nation enacts more far-reaching political and economic reforms.
Ronald D. Godard, a senior U.S. adviser for western hemisphere affairs, defended the embargo as a "one of the tools in our overall efforts to encourage respect for the human rights and basic freedoms to which the United Nations itself is committed."
"Cuba's resolution seeks to identify an external scapegoat for the island's economic problems when they are principally caused by the economic policies that Cuban government has pursued for the past half century," Godard said.
In Havana, as in years past, the run-up to the vote was marked with book launches and conferences discussing the embargo.
Officials released their latest tally of the sanctions' cumulative effect over five decades — just over $1 trillion in damage to the Cuban economy — a figure arrived at using a complex and some say flawed calculus factoring in things like interest and the decline of the dollar against the gold standard.
The Cuban Foreign Ministry kept up a constant stream of tweets during the U.N. session railing against what officials here refer to as the "blockade."
"The U.S. blockade is a permanent threat against the stability of a nation," the ministry tweeted.
Associated Press writer Peter Orsi in Havana contributed to this story.