He followed a conventional cursus honorum, following his uncle Girolamo Pamphili as auditor of the Rota, and like him, attaining the position of cardinal-priest of Sant'Eusebio.

He served as a consistorial lawyer in 1601, and in 1604 succeeded his uncle, Cardinal Girolamo Pamphili, as auditor of the Roman Rota, the ecclesiastical appellate tribunal.

They put up their own candidate (Giulio Cesare Sacchetti) but could not establish enough support for him and agreed to Cardinal Pamphili as an acceptable compromise, though he had served as legate to Spain.

The French Parlement of Paris declared the papal ordinance void in France, but Innocent X did not yield until Mazarin prepared to send troops to Italy.

This led to the formulary controversy, Blaise Pascal's writing of the Lettres Provinciales, and finally to the razing of the Jansenist convent of Port-Royal and the subsequent dissolving of its community.

Hostilities between the papacy and the Duchy of Parma resumed in 1649, and forces loyal to Pope Innocent X destroyed the city of Castro on 2 September 1649.

In 1650 Innocent X issued the papal brief Zelo Domus Dei[11] against the Peace of Westphalia, and backdated it to 1648 in order to preserve potential claims for confiscated land and property.

[13] Rinuccini hoped he could discourage the Confederates from allying with Charles I and the Royalists in the English Civil War and instead encourage them towards the foundation of an independent Catholic – ruled Ireland.

About 1635, at the height of the Thirty Years' War in Germany, in which the papacy was intricately involved, Cardinal Antonio commissioned Guido Reni's painting of the Archangel Michael, trampling Satan, who bears the recognizable features of Innocent X.

[14] This bold political artwork still hangs in a side chapel of the Capuchin friars' Church of the Conception (Santa Maria della Concezione dei Cappuccini) in Rome.

A legend related to the painting is that the dashing and high-living artist, Guido Reni, had been insulted by rumours he thought were circulated by Cardinal Pamphili.

This state of affairs was alluded to in the Encyclopædia Britannica 9th edition (1880): "Throughout his reign the influence exercised over him by Maidalchini, his deceased brother's wife, was very great, and such as to give rise to gross scandal, for which, however, there appears to have been no adequate ground....

The avarice of his female counsellor gave to his reign a tone of oppression and sordid greed which probably it would not otherwise have shown, for personally he was not without noble and reforming impulses.

On 8 January it was transferred to St. Peter's Basilica, where the sealing of the coffin was witnessed by Cardinals Niccolò Albergati-Ludovisi, Fabio Chigi, Luigi Omodei, Pietro Vito Ottoboni, Marcello Santacroce, Baccio Aldobrandini, Cristoforo Vidman, Lorenzo Raggi, Carlo Pio di Savoia and Gualtieri, Princes Pamphili, Ludovisi and Giustiniani, and the Master of Ceremonies Fulvio Servantio.

[25] Innocent's tomb is located in the Church of Sant'Agnese in Agone which he had built in 1652 adjacent to the family palace, the Palazzo Pamphili, in Rome.