President Barack Obama has said the US seeks a "new beginning" with Cuba and an "equal partnership" with all the nations of the Americas.
Obama was addressing Latin American and Caribbean leaders at the Summit of the Americas in Trinidad and Tobago.
The summit follows a thaw in US-Cuban relations. Cuba is not at the summit.
Earlier, US secretary of state Hillary Clinton welcomed an offer for talks from Cuban President Raul Castro, saying the old US policy had failed.
Castro said this weekend that he was ready to talk about "everything" with the US, including human rights, political prisoners and freedom of the press.
His comments came after the US eased its long-standing embargo of the communist nation, allowing Cuban- Americans to visit relatives in Cuba and send money home more easily.
Speaking to leaders gathered in Port of Spain, Obama declared: "The US seeks a new beginning with Cuba."
"I know there is a longer journey that must be travelled to overcome decades of mistrust, but there are critical steps we can take toward a new day," he said.
Cuba is excluded from the summit, which includes 34 members of the Organisation of American States (OAS), though Latin American leaders have been calling for the communist country to be readmitted.
The US has not maintained high-level diplomatic relations with Cuba since Fidel Castro led the island's revolution in 1960.
Washington imposed a trade embargo in the same year which has regularly been beefed up and backed by policies aimed at hastening the fall of the communist government.
Under former US President George W Bush, measures were put in place to support Cuban opposition and "hasten the end" of the Castro regime.
However, speaking on Friday in the Dominican Republic, Clinton acknowledged that US policy towards Cuba had "failed" and said Washington was "taking a very serious look at how to respond".
Addressing the summit, Obama said he wanted to move forward with a sense of "equal partnership" with all the nations of the Americas despite decades of mistrust.
"I am here to launch a new chapter of engagement that will be sustained throughout my administration," he said to applause from the delegates.