Born in Polizzi Generosa, Sicily, Rampolla was the son of Ignazio Rampolla, Count of Tindaro, and of his wife, Orsola Errante. He is often referred to with the title of marquess, but this appears to be inaccurate.
Rampolla was educated at the Collegio Capranica and the Pontifical Gregorian University. Having displayed a considerable knowledge in Oriental affairs, he was sent to the Pontifical Academy of Ecclesiastical Nobles as preparation for service in the Roman Curia.
In 1866 Rampolla was ordained a priest. In 1874 he was named a Canon of the Basilica di Santa Maria Maggiore. In 1875 he was sent to Spain as Auditor of the papal nunciature. In 1877 he returned to Rome and was named Secretary for Oriental Affairs of the Congregation for the Propagation of the Faith. The following year he was made a Protonotary apostolic de numero participantium. In 1880 he was named Secretary of the Congregation for the Propagation of the Faith, and then also Secretary of the Congregation of Extraordinary Ecclesiastical Affairs.
On 1 December 1882 Rampolla was appointed titular archbishop of Heraclea in Europa, and consecrated bishop by Edward Henry Cardinal Howard. This was in preparation for his nomination as papal nuncio to Spain several weeks later.
On 14 March 1887 Pope Leo XIII created Rampolla a Cardinal-Priest of Santa Cecilia in Trastevere. On 2 June he was appointed Secretary of State. In this office (as previously in Spain), Rampolla employed Giacomo della Chiesa, the future Benedict XV, as his secretary.
When Leo XIII died in 1903, it was widely expected that Rampolla would be elected pope. His candidacy gained momentum until the last moment, but the Austrian Emperor Francis Joseph I (one of the three Catholic powers with pretensions to such a capacity) imposed a veto, the "Jus Exclusivæ", right in the middle of the Conclave, through the agency of Cardinal Jan Puzyna de Kosielsko, Prince-Archbishop of Kraków, who was subsequently awarded the highest Austro-Hungarian decoration, the Grand Cross of State. The Austrian Cardinal Anton Josef Gruscha refused to express the veto of his emperor, who turned then to the Polish Cardinal of Krakow. The Polish cardinal was booed by the others with pudeat te pudeat te, shame on you shame on you, when he announced the veto. 
Conclave Secretary Rafael Merry del Val reported later that Cardinal Jan Puzyna de Kosielsko of Krakow came to see him, demanding to announce his veto against Cardinal Rampolla in the name of Emperor Franz Joseph I of Austria of Austria-Hungary. Merry Del Val protested and refused to even accept the document, which, in the heat of the debate fell on the floor and was picked up by Jan Puzyna de Kosielsko himself, as the young Monsignore refused to bend down and touch such a document.  Rampolla, according to Merry del Val, actually gained votes after the veto. Later, Merry del Val opined to Ludwig von Pastor that Rampolla never had a chance, because the cardinals wanted a new direction after the pontificate of Pope Leo XIII. 
The reasons for Austria's opposition have never been clarified. Possibly, the veto was a result of the pro-French positions adopted by Rampolla, positions which reflected the policies of Leo XIII. Part of the Holy See's unsuccessful policy involving France was the attempted reconciliation of French Catholics with their nation's republican government. Informed sources at the time claimed that Austria acted on behalf of Italy's government through the intervention of State Minister Zanardelli 
While formally protesting this intrusion, the Cardinals recognized the existing legal right of the emperor and would not specifically offend such a prominent Catholic power, and support for Rampolla dissipated, leading to the election of Giuseppe Sarto as Pope Pius X. Explicitly abolishing any veto rights was one of the new Pope's first official acts.
Pius X chose the secretary of the conclave that had elected him, Rafael Merry del Val, to succeed Rampolla as Secretary of State. Rampolla was appointed Arch-Priest of Saint Peter, what is called today Fabric of Saint Peter  He lived in a modest house behind Saint Peter Basilica. In 1912, he was appointed also as Archivist of the Holy Roman Church, a minor position he held until his death. Symbolizing successful papal diplomacy and world-wide contacts, he continued to be viewed as a most likely successor to Pope Pius X in case of Pius X's death. Rampolla died suddenly in Rome on December 16, 1913 at age seventy, some months before the pope died in August 1914.  His friend and closest collaborator, Cardinal Giacomo della Chiesa, presided over his funeral ceremonies and a few months later was elected as Pope Benedict XV.
- Burkle-Young, Francis A. (2000). Papal Elections in the Age of Transition 1878-1922. Lanham: Lexington Books.
- Lonyay, Graf Karoly (1950). Rudolf; the tragedy of Mayerling. London: H. Hamilton.
- Various (1967). The World Book Encyclopaedia:Q-R (Volume 16).
- Waal, Anton de (1915). Benedict XV. Hamm: Breer & Thiemann.
|Catholic Church titles|
|Cardinal Secretary of State|
| Succeeded by|
Rafael Merry del Val
Gaetano Aloisi Masella
|Camerlengo of the Sacred College of Cardinals|
16 January 1893-18 May 1894
| Succeeded by|
Fulco Luigi Ruffo-Scilla
Francesco Salesio Della Volpe
|Archivist of the Holy Roman Church|
1912 - 16 December 1913
| Succeeded by|
Francesco di Paola Cassetta