Sitting around an oval table with some 30 other regional leaders in Panama City, Obama and Castro spoke one after the other in an unprecedented public exchange between the leaders of the Cold War-era foes.
"This shift in US policy represents a turning point for our entire region," Obama said. "The fact that President Castro and I are both sitting here today marks a historic occasion."
As the US leader looked on, Castro declared: "President Obama is an honest man."
Obama cited the human rights situation in Cuba, while Castro renewed calls for the US Congress to lift a decades-old embargo.
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"I think it's no secret, President Castro I'm sure would agree, that there will continue to be significant differences between our two countries," Obama said.
Taking their bid to restore diplomatic ties to a new level, Obama and Castro will have a discussion on the sidelines of the second and final day of the summit.
The face-to-face talks will be the climax of their surprise announcement on December 17 that, after 18 months of secret negotiations, they would seek to normalize relations between their two nations.
It is Cuba's first time participating at the 21-year-old summit.
Colombian President Juan Manuel Santos summed up the mood, saying "an old obstacle in relations between Latin America and North America is being removed.