In 1899 Granito Pignatelli di Belmonte was appointed Titular Archbishop of Edessa, consecrated by Mariano Rampolla, Cardinal Secretary of State, in Rome.

Pius X created him Cardinal-Priest in the Consistory of 27 November 1911, giving him the title of Santa Maria degli Angeli.

On 14 July that year the new Dean was also appointed Prefect of the Congregation of Ceremonies by Pope Pius XI.

The Cardinal was appointed Grand Prior of Rome of the Sovereign Military Order of Malta from December 1937.

In 1911 he was granted the Grand Cross of the Order of Saint Stephen of Hungary by Emperor Franz Joseph I of Austria.