Italian lay woman Francesca Di Giovanni (66) will assume a newly created post in a division known as the Section for Relations with States where she takes the rank of under-secretary, effectively one of two deputy foreign ministers.
The Vatican announced on Wednesday that within the Vatican Secretariat of State's Section for Relations with States, Di Giovanni will head the multilateral sector, which deals with intergovernmental organizations and multilateral treaties.
Born in Palermo, Di Giovanni earned a law degree and began working as an official at the Section for Relations with States in 1993, focusing her work on issues such as "migrants and refugees, worldwide humanitarian law, communications, private global law, the status of women, intellectual property, and tourism", the Vatican said.
The Secretariat of State deals with the city-state's operations and diplomatic affairs.Di Giovanni will be the first person to hold this particular position.
"I hope that my being a woman might reflect itself positively in this task, even if they are gifts that I certainly find in my male colleagues as well", she said.
"But the responsibility is connected to the job, rather than to the fact of being a woman", she added.
The move comes as Francis has called for women to be given greater decision-making roles in the male-dominated Vatican.
The Vatican, a sovereign state surrounded by Rome, has diplomatic relations with more than 180 countries.
Elsewhere, he's appointed two female undersecretaries at the Dicastery for Laity, Family and Life, a woman undersecretary at the religious life department and the first female deputy director of the Holy See Press Office, Paloma Garcia Ovejero - although she resigned her position at the end of past year. Mary Ann Hinsdale, a professor of theology at Boston College, cheered the appointment of Di Giovanni.
The Pope has also made provisions for those who are not priests to hold one of the top two positions in some Vatican departments, of prefect or secretary.
"My hope is that his action might signal future appointments of talented, capable women to other Vatican dicasteries and departments", Hinsdale told the National Catholic Reporter.