The Vatican began a new chapter ahead of key reforms on Tuesday as veteran diplomat Pietro Parolin replaced scandal-hit cardinal Tarcisio Bertone as right-hand man to Pope Francis.
The Secretary of State, frequently referred to as the Vatican "prime minister", is an influential post and will have added significance as Francis attempts to overhaul the Church's government.
The formal handover of power was due at a ceremony in the Vatican later on Tuesday with the top officials from the Secretariat of State.
Parolin up until now has been the Vatican envoy to Venezuela and at 58 is considered young for a top Roman Catholic Church posting.
He is the youngest cleric to occupy the post since Eugenio Pacelli, another diplomat who was appointed secretary of state in 1930 at the age of 53 and went on to become Pius XII.
Parolin was previously a Vatican envoy to Mexico and Nigeria and has worked on sensitive issues for the Church, including diplomatic relations with Israel.
The secretary of state is considered the top political and diplomatic position in the Vatican and in some instances he can stand in for the pope.
Three secretaries have gone on to be popes.
"He is an excellent choice, an efficient man, a good negotiator, very balanced," French cardinal Jean-Louis Tauran, a former diplomatic chief for pope John Paul II, said on Vatican radio.
Parolin was ordained in 1980 and his first foreign posting for the Vatican was in Nigeria in 1986, followed by Mexico in 1989 where he fought to gain legal recognition for the Catholic Church.
In 1992, he was called back to Rome to work for the Secretariat of State and was appointed to a position equivalent to a deputy foreign minister in 2002.
In 2009, he was appointed papal nuncio to Caracas.
The outgoing Bertone was appointed in 2006 by Benedict XVI.
He was heavily criticised for his management style and was the chief target of the intrigue and sleaze allegations in confidential Vatican papers that were leaked in the Italian press last year.
Parolin takes over at a time in which the pope is mulling a reform in the way the Church is run.
Francis has formed an unprecedented council of eight cardinals from around the world to advise him on reforms.