Pope Francis is on his way to Cuba on a visit which will also include the United States.
In his now trademark style, Francis carried his personal leather briefcase as he greeted a farewell delegation and walked up the aeroplane steps.
The Pope will spend four days in Cuba before flying to the United States. He is visiting both countries for the first time as pontiff, after Vatican mediation that led to a restoration of ties between Washington and Havana last year.
The Vatican said ahead of the visit they hoped Francis' trip to Cuba would help bring an end to a 53-year-old U.S. embargo and lead to more freedom and human rights on the communist island.
Meanwhile, when Francis arrives in Washington next week, the White House hopes he will bring attention to the need to curb climate change and fight inequality - areas of common ground for the popular pontiff and President Barack Obama.