The pontiff played a key role in bringing them together, after he sent private letters to Barack Obama and Raúl Castro earlier this year.
He also hosted secret talks at the Vatican in October in an attempt to end decades of hostility.
The presidents have announced the re-establishment of diplomatic ties with the exchange of prisoners.
It's thought Cardinal Jaime Ortega played a significant role in negotiations for the release of American aid worker Alan Gross, who was freed after five years in a Cuban prison.
The White House is taking steps to relax travel, diplomatic and trade restrictions, while Cuba is releasing Americans and other dissidents being held in Havana.
The process, which is understood to have taken around 18 months, will end more than 50 years of isolation.
A senior Obama official said that when the US president met Pope Francis, "Cuba got as much attention as anything else discussed", adding:
"The support of Pope Francis and the support of the Vatican was important to us."
The Vatican also released a statement shortly after the agreements were officially announced:
"The Holy Father wishes to express his warm congratulations for the historic decision taken by the governments of the United States of America and Cuba to establish diplomatic relations, with the aim of overcoming in the interest of the citizens of both countries, the difficulties which have marked their recent history."