The almost-ritual UN debate saw Cuban Foreign Minister Bruno Rodriguez lash out at what he called "the inhuman, failed and anachronistic policy of 11 successive US administrations" since the full embargo was imposed in 1962.
United States reaffirmed that while $2 billion in remittances had been sent to the Communist-ruled island by Cuban Americans in 2011, it would only ease the embargo when Cuba carries out major social and economic changes.
The vote in favor rose from 186 for the 20th anniversary resolution last year. This time the United States, Israel and Palau opposed the resolution while the Marshall Islands and Micronesia abstained.
Rodriguez said US President Barack Obama had offered a new beginning with Cuba when he first came to power in 2008. "However the reality of the last four years has been characterized by a persistent tightening of the economic, commercial and financial embargo," he told the 193-member assembly.
The minister said Cuban hospitals could not get heart and anti-cancer medicines as he restated his government's annual charge that the US sanctions amount to "genocide."
"There is no legitimate or moral reason to maintain this embargo which is anchored in the Cold War," Rodriguez argued.
Russia, China, Organization of Islamic Cooperation member states and the Non-Aligned movement all spoke out against the embargo.
US diplomat Ronald Godard said the Cuban-proposed resolution seeks to "identify an external scapegoat for the island's economic problems."
Godard highlighted the case of an American Alan Gross, imprisoned in Cuba since 2009 for taking computers and satellite phones for the island's small Jewish community. Cuba has said Gross was a spy.
Godard told the assembly that politically motivated short-term detentions this year had already surpassed the 4,000 recorded in 2011.
"The international community cannot in good conscience ignore the ease and frequency with which the Cuban regime silences critics, disputes peaceful assembly and impedes independent journalism," Godard said.
The Obama administration wanted to "empower Cubans" by allowing easier contacts between Cubans and Americans, Godard said. On top of remittances sent back, Godard said $1.2 billion in private humanitarian assistance was allowed in 2011.
Cuba was not a major issue in this year's US presidential election.