Pope Francis is leaving the Vatican on Saturday to become the US ambassador to the United States.
Cardinal Angelo Scola will be in charge of the US Embassy in Rome.
He replaces Cardinal Peter Turkson, who has been in the post since January.
US President Donald Trump appointed the US Cardinal in January as a permanent representative of the Vatican.
The Vatican has repeatedly refused to recognize the pope’s election as the Pope.
Trump has said that the Pope is a fake, a fraud, and an enemy of the United Nations.
The cardinal is not the first pontiff to leave the Vatican after taking office.
In February, Pope Benedict XVI departed after a two-and-a-half year tenure.
Pope Francis is a Catholic who is considered the most conservative pope in the world.
He has frequently criticized Pope Francis for his anti-immigrant, anti-Muslim, and anti-gay positions, and has been seen as being a threat to Catholic institutions and practices.
Scola, who is known for his conservative stance on immigration, will be the second Jesuit cardinal to serve in the US, after Cardinal Carlo Maria Viganò, who served as the US Bishop of New York from 2011 to 2016.
In a statement on his Twitter account, Scola said he is “delighted” to be a “part of the American community,” and added that “this is my great honor.”
“I am grateful to the Vatican and all of its people for the opportunity to serve, and to all of my Catholic brothers and sisters, for all their work to make this country and the world a better place,” he said.
A US-based Catholic newspaper, The Wall Street Journal, said the resignation of Pope Francis will be a blow to the church.
“The departure of Cardinal Scola could be seen as a signal that the Vatican is not yet ready to accept the pope,” the newspaper said.
“The Vatican, and the Catholic Church more broadly, is a world leader in promoting and protecting the rights of women, children, immigrants, people of faith, and all other peoples,” it added.
Pope Francis has often praised the US and Pope Trump, calling him a great and faithful servant.
He called the president a “true friend.”
“I thank God for all of you who have supported me and my administration, and I thank God that I am a Christian and a man of God,” he told the American people during a January visit to the U.S. The pope also made a statement at the Vatican that said he hopes to have a meeting with Trump in the coming months.