Prince Don Domenico Pignatelli di Belmonte was born on 19 November 1730 in Naples, Italy, the son of Princess Donna Anna Francesca, Princess of Belmonte in her own right and 1st Princess of the Holy Roman Empire by marriage. She was daughter and heiress of the 5th Prince, and as such was a Grandee of Spain 1st Class, 5th Duchess of Acerenza, 8th Marchioness of Galatone, 5th Countess of Copertino, 7th Baroness of Badolato, Signore di Veglie, Leverano, San Cosimo etc. Prince Don Domenico Pignatelli di Belmonte's father was Prince Don Antonio Pignatelli y Aymerich, who was also 2nd Marquess of San Vicente and 3rd Marquess of Argençola, and General of the Imperial Cavalry. He was General Commander of the Austrian Army at the Battle of Bitonto in 1734, during the War of Polish Succession, and was created a Knight of the Golden Fleece in 1735, a Knight of the Order of Santiago and a Knight of the Illustrious Royal Order of St. Januarius . Domenico Pignatelli di Belmonte's aunt on his father's side, Doña Marianna, Countess of Althann, was lady in waiting to the Empress Elizabeth, consort of Emperor Charles VI and the mother of Empress Maria Theresa of Austria. Domenico Pignatelli di Belmonte was ordained priest as a member of the Congregation of Clerks Regular of the Divine Providence, as Father Domenico Pignatelli on 22 September 1753. He was appointed Lector of Sacred Canons in the House of Studies of SS. Apostoli, Naples, on 12 December 1755. Thereafter he was appointed, variously, Secretary to the Superior General, Superior of SS. Apostoli, Procurator General, and Co-Adjustor to Father Antonio Francesco Vezzosi, the Superior General of the Theatine Order, on 31 May 1774. He was himself appointed Superior General on 22 April 1777. He was appointed as Examiner of those appointed to Ecclesiastical Chairs. In his Episcopate, he was elected Bishop of Caserta and chosen as Assistant at the Pontifical Throne on 25 February 1782. He was subsequently consecrated Bishop on 3 March 1782 in Rome, at the church of San Silvestro al Monte, by Cardinal Innocenzo Conti, Secretary of the Chancery of Apostolic Briefs, who was assisted in the ceremony by Girolamo Volpi, Titular Archbishop of Neocesarea, and by François de Pierre de Bernis, Titular Bishop of Apollonia, Vicar General of Albi. Bishop Domenico was General of the Congregation of Clerks Regular of the Divine Providence. He was promoted to the Metropolitan See of Palermo and Monreale on 29 March 1802, and received the pallium on the same day. He was Viceroy of Sicily, 1802-1803, during the brief reign of King Ferdinand IV. He was created a Cardinal Priest in the consistory of 9 August 1802, and received the red biretta on 5 December 1802, in the chapel of the Seminary of Palermo. He was created a cardinal in place of Paulo Luis Silva, assessor of the Supreme Sacred Congregation of the Roman and Universal Inquisition, who had been created and reserved In pectore in the consistory of 23 February 1801 and died before his name was published. Cardinal Domenico was Grand Prior of the Sacred Military Constantinian Order of Saint George, and held the rank of Knight Grand Cross of that Order. He was Knighted in the Illustrious Royal Order of St. Januarius. Cardinal Domenico died of gout before receiving the red hat and title of his cardinalate, and was buried in the church of the Congregation of Clerks Regular of the Divine Providence, in Palermo.