The first regularly scheduled commercial flight between the US and Cuba in more than half a century departed on Wednesday.

The first of several US carriers to begin serving Cuba in the coming months, JetBlue Airways was due to fly from Fort Lauderdale, Florida, to Santa Clara, a central city known for its monument to revolutionary leader Ernesto "Che" Guevara.

US Transportation Secretary Anthony Foxx, JetBlue chief executive officer Robin Hayes, other officials and journalists were set to travel on the 150-seat Airbus A320. Regular travellers, including some of Cuban descent, were to occupy nearly half the seats on a route that may be a commercial challenge, at least initially.

Lázaro Chavez, a 49-year-old pharmacist who lives in Miami and returns frequently to his homeland, said at the Fort Lauderdale airport that he was taking the flight for two reasons. "One, I am going to see my family. Two, I want to be on this historic flight."

Cuba and the US began normalising relations in December 2014 after 18 months of secret talks and have since restored full diplomatic ties. The countries had been hostile for more than five decades, since Fidel Castro ousted US-backed dictator Fulgencio Batista in a 1959 revolution that steered the island on a communist course and made it a close ally of the Soviet Union.

Despite the opening, which has included a landmark visit to the Caribbean island by Obama in March, the US president has been unable to persuade Congress to lift a longstanding trade embargo on Cuba.

US citizens are still prohibited from visiting as tourists, although there have long been exceptions to the ban, ranging from visiting family to business, cultural, religious and educational travel. The Obama administration has further eased the restrictions.

Despite the travel limitations, US airlines have rushed to start flights - adding a lot of capacity and setting themselves up to lose money on the trips in the short run, said industry consultant Robert Mann.

"Most carriers look at international markets that have been restricted and are just opening up as an investment," Mann said. "You need to get your foot in the door."

Services on regional carrier Silver Airways and American Airlines Group from the Miami-Fort Lauderdale area to Cuba's outlying provinces are the next to start, in September. Three other carriers will follow.

Mann said the companies probably offered to fly to Cuban cities that are unfamiliar to many American travellers, so that US officials would look favorably on their applications to fly to Havana.

A memorandum of understanding between Cuba and the US will limit Havana flights to 20 round trips per day. US officials have yet to announce a final decision on which companies will get those coveted routes.

"The Havana competition was one of the most over-subscribed competitions that I've been a part of," Foxx said in an interview. "I think that speaks to the interest on the part of the American people, and it also speaks to the level of commercial interest in the US that exists." - Reuters