U.S. President Barack Obama and Cuban President Raul Castro shook hands at the Summit of the Americas in Panama on April 10.
A photograph showed Obama and Castro chatting in a small group of leaders at the summit's opening ceremony in Panama City.
A White House official confirmed the two men shook hands and spoke briefly.
"This was an informal interaction and there was not a substantive conversation between the two leaders," the official said.
Obama and Castro are expected to meet again on April 11 and talk about their efforts to restore full diplomatic relations and boost trade and travel between the two countries.
Obama and Castro announced plans to restore diplomatic relations in December.
The handshake was described by the U.S. State Department as "an informal interaction" between the two leaders.
Apart from several informal meetings, U.S. and Cuban leaders have not had any significant encounters since Castro's older brother, Fidel, deposed U.S.-backed dictator Fulgencio Batista in 1959.
Meanwhile, U.S. Secretary of State John Kerry met Cuban Foreign Minister Bruno Rodriguez for closed-door talks in Panama City on April 9,the first meeting between the two countries' top diplomats since 1958.
A senior U.S. State Department official said it was a "lengthy and very constructive discussion" and that they made progress.
Colombian President Juan Manuel Santos hailed Obama's push to improve relations with Cuba, saying it was helping to heal a "blister" that was hurting the region.
However, Cuban dissident Guillermo Farinas said civic groups in Cuba have been sidelined from talks and appealed to Obama to support their push for more democracy.
"The Cuban government is showing no goodwill ... They don't want to make any kind of concessions," he told the Reuters news agency.
Obama appears to be close to removing communist-run Cuba from a U.S. list of countries that it says sponsor terrorism.
The State Department has now recommended that Cuba be taken off the terrorism list, a U.S. Senate Foreign Relations Committee aide said.
Obama is expected to agree, although it is unclear when.
Cuba's inclusion on the list subjects it to a series of automatic U.S. sanctions and Havana is insisting it be reversed as a condition for restoring diplomatic ties.