Pope Alexander VIII elevated him to the cardinalate in 1690 despite his protests and made him the Cardinal-Deacon of Santa Maria in Aquiro but he later opted for the Diaconia of Sant'Adriano al Foro and later, as the Cardinal-Priest, for the titulus of San Silvestro in Capite.

In 1703 Pope Clement XI ordered a synod of Catholic bishops in northern Albania that discussed promotion of the Council of Trent decrees within Albanian dioceses, stemming conversions among locals to Islam and securing agreement to deny communion to crypto-Catholics who outwardly professed the Muslim faith.

[1][7][2] Despite initially holding an ambiguous neutrality in world affairs, Clement XI was later forced to name Charles, Archduke of Austria, as the King of Spain, since the imperial army had conquered much of northern Italy and was threatening Rome itself in January 1709.

The bull, which was produced with the contribution of Gregorio Selleri, a lector at the College of Saint Thomas, the future Pontifical University of Saint Thomas Aquinas Angelicum,[8] condemned Jansenism by extracting and anathematizing as heretical 101 propositions from the works of Pasquier Quesnel, declaring them to be identical in substance with propositions already condemned in the writings of Jansenius.

Because the local governments did not officially receive the bull, it was not, technically, in force in those areas – an example of the interference of states in religious affairs common before the 20th century.

Clement XI supported James Francis Edward Stuart, the exiled Stuart Prince of Wales, recognizing him as James III and VIII, and paid for the residence of him and his wife, Princess Maria Clementina Sobieska, Granddaughter of John III Sobieski, King of Poland-Lithuania, in Rome, the Palazzo Muti, as well as donating a summerhouse near the shores of Lake Albano.

[9] During his reign as a pope the famous Illyricum Sacrum was commissioned, and today it is one of the main sources of the field of Balkan region during Middle Ages, with over 5,000 pages divided in several volumes written by the Jesuit Daniele Farlati and Dom Jacopo Coleti.

He formally beatified a number of individuals: Alexis Falconieri, Bartholomew degli Amidei and Benedict Dellantella, (1 December 1717) and John Francis Régis (24 May 1716).

He canonized Andrew Avellino, Catherine of Bologna, Felix of Cantalice and Pope Pius V on 22 May 1712, Humility on 27 January 1720, Stephen of Obazine in 1701 and Boniface of Lausanne in 1702.

Clement XI died in Rome on 19 March 1721 at 12:45pm and was buried in the pavement of Saint Peter's Basilica rather than in an ornate tomb like those of his predecessors.

[11] The following day, Clement XI celebrated Mass in his private chapel before meeting various prelates which included the Archbishop of Ravenna Geronimo Crispi.

However, at around noon, he was suddenly struck with an extraordinary chill which was accompanied by a very strong fever that immediately forced him to his bed, with the pope declining a meal that evening.

[11] In his book "Journal of a Soul", while he was preparing for the Second Vatican Council, Pope John XXIII resolved to pray the Universal Prayer and highly recommended it to others.

Pope Clement XI had a famous sundial added in the church of Santa Maria degli Angeli e dei Martiri and had an obelisk erected in the Piazza della Rotonda in front of the Pantheon, and a port built on the Tiber River, the beautiful Porto di Ripetta, demolished at the end of the 19th century.