Leaders from across the Americas launched talks on expanding trade as the United States came under strong pressure to let Cuba attend future summits.
Colombian President Juan Manuel Santos, host of the Summit of the Americas, said Saturday it would be "unacceptable" to keep Cuba out of the next gathering.
"The isolation, the indifference has shown its ineffectiveness. In today's world, there is no justification for this anachronism," he stressed.
Cuba has never taken part in a Summit of the Americas, a regular meeting sponsored by the US-based Organization of American States (OAS).
Washington argues that communist-ruled Cuba is ineligible to attend because it lacks democratic credentials and does not "respect the human rights of the Cuban people."
Cuba was expelled from the OAS in 1962 at the height of the Cold War. The expulsion was rescinded in 2009, but Cuba has refused to return to the organization.
Ecuadoran President Rafael Correa is boycotting the summit because of the exclusion of Cuba, one of its allies and the Americas' only one-party Communist state.
Saturday, an alliance of left-leaning Latin American countries known as ALBA announced here that its members would not take part in any future summits of the Americas if Cuba was not included.
"We express our decision not to take part in future Summits of the Americas without the presence of Cuba," ALBA, which groups Venezuela, Ecuador, Bolivia, Nicaragua, Cuba, Antigua and Barbuda, and Saint Vincent and the Grenadines, said in a statement.
It also demanded an immediate end to Washington's 50-year-old "inhuman economic, trade and financial embargo against Cuba" and urged regional countries "to continue to maintain its united solidarity in favor of Cuba's admission to the summit".
The two-day summit formally opened earlier Saturday under tight security in this Colombian Caribbean resort city, attended by US President Barack Obama and 30 other democratically elected leaders of the Western Hemisphere.
"It is remarkable to see the changes that have been taking place in a relatively short period of time in Latin, Central America and in the Caribbean," the US leader said at a business forum ahead of the summit. "We've seen enormous progress.
But Brazilian President Dilma Rousseff, speaking at the same forum, urged Obama to treat Latin America as an equal.
"In Latin America, we have a huge space to make our relationship one of partnership, but partnership between equals," said Rousseff, whose country has gained mounting international clout as the world's sixth largest economy and Latin America's dominant power.
"This is a very relevant factor between the most developed country of the region and Latin American countries," she added, in veiled criticism of Washington's past dealings with an area it used to view as its own back yard.
Acknowledging the region's growing assertiveness and independence, Obama said in response: "I think often times in the press the focus is on controversies. Sometime those controversies date back to before I was born ... to the 1950's ... Yankees and the Cold War, and this and that.
"That is not the world in which we are living today," the US leader said. "My hope is that we all recognize this enormous opportunity that we have."
In addition to Cuba, many Latin American leaders sought to focus on the pros and cons of drug legalization.
Several Central American leaders met here on the sidelines of the summit to discuss Guatemala's proposal to consider legalizing street drug consumption. But they failed to reach consensus.
Guatemalan President Otto Perez insisted that his idea remained very much alive and voiced hope it would be taken up at a private meeting of hemispheric leaders.
Speaking at the business forum, Obama meanwhile said he favored a debate on the issue. On Friday, he said he opposed decriminalization or legalization of drugs.
"I think it is a valuable agenda to have a conversation whether the laws in place are laws that are doing more harm than good in certain places," the US leader said Saturday.
Venezuelan President Hugo Chavez, who is suffering from cancer, did not make the trip to Cartagena on the advice of his doctors. He was to travel to Cuba for further radiation therapy to treat a recurrence of cancer, according to his foreign minister Nicolas Maduro.
Also absent was Nicaraguan President Daniel Ortega, Honduran President Porfirio Lobo said. No reason was immediately given.
In the fallout of an embarrassing incident, the US Secret Service said Saturday it had suspended 11 agents assigned to Obama's trip to Colombia amid reports they had used prostitutes.
Five US military personnel are also being investigated for misconduct said to have taken place at the same hotel where the Secret Service staff were staying in Cartagena, and have been confined to barracks.