The Secretariat of State (Latin: Secretaria Status; Italian: Segreteria di Stato) is the oldest dicastery in the Roman Curia, the central papal governing bureaucracy of the Catholic Church. It is headed by the Cardinal Secretary of State and performs all the political and diplomatic functions of the Holy See. The Secretariat is divided into three sections: the Section for General Affairs, the Section for Relations with States, and, since 2017, the Section for Diplomatic Staff.

The origins of the Secretariat of State go back to the fifteenth century. The apostolic constitution Non Debet Reprehensibile of 31 December 1487 established the Secretaria Apostolica comprising twenty-four apostolic secretaries, one of whom bore the title Secretarius Domesticus and held a position of pre-eminence. One can also trace to this Secretaria Apostolica the Chancery of Briefs, the Secretariat of Briefs to Princes and the Secretariat of Latin Letters.

Pope Leo X established another position, the Secretarius Intimus, to assist the Cardinal who had control of the affairs of State and to attend to correspondence in languages other than Latin, chiefly with the Apostolic Nuncios (who at that time were evolving into permanent diplomatic representatives). From these beginnings, the Secretariat of State developed, especially at the time of the Council of Trent.

For a long time, the Secretarius Intimus, also called Secretarius Papae or Secretarius Maior, was almost always a prelate, often endowed with episcopal rank. It was only at the beginning of the pontificate of Innocent X that someone already a Cardinal and not a member of the Pope's family was called to this high office. Pope Innocent XII definitively abolished the office of Cardinal Nephew, and the powers of that office were assigned to the Cardinal Secretary of State alone.

On 19 July 1814, Pope Pius VII established the Sacred Congregation for the Extraordinary Ecclesiastical Affairs, expanding the Congregatio super negotiis ecclesiasticis Regni Galliarum established by Pius VI in 1793. With the apostolic constitution Sapienti Consilio of 29 June 1908, Saint Pius X divided the Sacred Congregation for Extraordinary Ecclesiastical Affairs in the form fixed by the Codex Iuris Canonici of 1917 (Can. 263) and he specified the duties of each of the three sections: the first was concerned essentially with extraordinary affairs, while the second attended to the ordinary affairs, and the third, until then an independent body (the Chancery of Apostolic Briefs), had the duty of preparing and dispatching pontifical Briefs.

With the apostolic constitution Regimini Ecclesiae universae of 15 August 1967, Pope Paul VI reformed the Roman Curia, implementing the desire expressed by the bishops in the Second Vatican Council. This gave a new face to the Secretariat of State, suppressing the Chancery of Apostolic Briefs, formerly the third section, and transforming the former first section, the Sacred Congregation for the Extraordinary Ecclesiastical Affairs, into a body distinct from the Secretariat of State, though closely related to it, which was to be known as the Council for the Public Affairs of the Church.

In December 2020, Pope Francis enacted legislation stripping the Secretariat of State of its financial assets and real estate holdings following its bungled management of hundreds of millions of euros in donations. Controversial investments which were made by the Vatican Secretariat of State department also became subject to a corruption investigation.

On 28 June 1988, John Paul II promulgated the apostolic constitution Pastor bonus, which introduced a reform of the Roman Curia and divided the Secretariat of State into two sections: the Section for General Affairs and the Section for Relations with States, which incorporated the Council for the Public Affairs of the Church. Pope Francis added a third unit, the Section for Diplomatic Staff, in November 2017.