JetBlue Flight 387 took off en route to Cuba from Fort Lauderdale, Florida, the first direct commercial flight between the US and the island in more than a half-century.
The flight is the latest symbol of the thawing of relations between the former Cold War adversaries, who restored diplomatic ties in 2015.
Soon, up to a maximum of 110 daily flights operated by such carriers as JetBlue, American Airlines, Delta, Frontier, Southwest and Silver Airways are due to begin flying to the communist-run island, according to the US Department of Transportation.
Tourism to Cuba is still illegal for Americans, but there are now 12 categories of “authorized travel.”