Pope Clement IX established the Congregation for Indulgences and Sacred Relics in his apostolic letter In ipsis pontificatus nostra primordiis on 6 July 1669, giving permanent form to a commission of cardinals created on 4 August 1667. Initially the Congregation had a purely disciplinary character overseeing the application and observance of the decree Council of Trent's decree De indulgentiis issued on 3-4 December 1563 and limiting the abuses introduced in the distribution of indulgences by the Secretariat of the Briefs.
The Congregation also managed the authentication of relics, particularly when disputes were addressed in legal proceedings. The Congregation had its own staff of theologians and archaeologists, mostly Jesuits or Capuchins, to help resolve complex questions.
At the beginning of the eighteenth century, the Congregation began to distribute indulgences itself, a privilege that was recognized by Pope Benedict XIV in 1742. Conflicts of jurisdiction and rival interests arose between the Congregation and the Secretariat of the Briefs until Pope Pius IX, with his motu proprio Fidelis domus Domini of 2 January 1855, deprived the Congregation of the rights Benedict XIV had granted it. Pius IX's instructions were reiterated with greater force by Pope Leo XIII in the motu proprio Christianae reipublicae of 31 October 1897.
On 28 January 1904, with the motu proprio Quae in Ecclesiae, Pope Pius X united the Congregation with the Congregation of Rites, and on that same day he made Cardinal Luigi Tripepi, who had been Prefect of the Congregation of Indulgences and Sacred Relics since 7 January 1903, also the Pro-Prefect of the Congregation of Rites.
On 29 June 1908, with the apostolic constitution Sapienti consilio, Pius X suppressed the Congregation and transferred its responsibilities for indulgences to the Holy Office. Finally, Pope Benedict XV on 25 March 1917, with the motu proprio Alloquentes proxime, assigned those responsibilities to the Apostolic Penitentiary.