Nearly 50 years after service between the islands was severed due to bad blood between Washington and Havana, flights are now available between the two countries.
A Cuban travel official says the American Eagle charter flight from San Juan is arriving in the eastern city of Santiago on Friday.
Elizza Cabezas says the passengers are mostly Puerto Rico residents of Cuban origin visiting relatives back home.
The U.S. embargo has prohibited most American citizens from traveling to Cuba since the 1960s.
President Barack Obama has relaxed some restrictions. Cuban-Americans can now make unlimited family visits.
The U.S. has also authorized more airports to handle Cuba flights. Previously they all went through Miami, New York or Los Angeles.
Based on reporting by the Associated Press