Cuban Foreign Minister Bruno Rodriguez and Secretary of State John Kerry held closed-door discussions in Panama, in the highest level meeting between the two countries in more than half a century.
Meanwhile, the US state department has reportedly recommended that Cuba be removed from its list of states said to sponsor terrorism.
Such a move could pave the way for the two countries re-opening embassies.
President Barack Obama and his Cuban counterpart Raul Castro are also due to hold their first formal meeting at the Summit of the Americas in Panama over the coming days.
Few details have emerged from the meeting between John Kerry and Bruno Rodriguez. The last comparable high-level meeting was in 1959, when Fidel Castro met then Vice-President Richard Nixon.
Diplomatic ties froze two years later, but last year Barack Obama announced that a “new chapter” in relations would commence.
Meanwhile Senator Ben Cardin, a leading member of the Senate Foreign Affairs Committee, said the US State Department had recommended removing Cuba from the list of state sponsors of terrorism.
The move was “the result of a months-long technical review” and would be “an important step forward in our efforts to forge a more fruitful relationship with Cuba”, he said.
Cuba is one of four countries still on the US list of countries accused of repeatedly supporting global terrorism; Iran, Sudan and Syria are others.
The communist country was first put on the list in 1982 for offering sanctuary to militant ETA Basque separatists and Colombian Farc rebels.
Removing Cuba from the list could lead to the easing of financial restrictions on Cuba’s access to loans and aid.
If Barack Obama opts to accept the state department’s recommendations, Congress would have 45 days to decide whether to override him.
The president faces fierce critics of his Cuban policy at home, such as from Cuban-American Ted Cruz, who is a Republican presidential candidate.
Correspondents say removing Cuba from the list of state sponsors of terrorism will throw a stark light on the US’s relations with Venezuela.
The Venezuelan President Nicolas Maduro hopes to bring a petition signed by 10 million of his citizens urging Barack Obama to remove an order imposing sanctions against seven Venezuelan officials accused of human rights abuses in an opposition crackdown.
Venezuela has many friends at the summit and other Latin American nations have criticized the order, which calls Caracas a US national security threat.
Barack Obama has tried to reduce tensions with Venezuela ahead of the summit, saying the US did not perceive the country as a threat.
