He was born in Florence to Carlo Barberini and Costanza Magalotti, and studied at the University of Pisa,[2] graduating in canon and civil law in 1623.

His uncle, Maffeo Barberini, newly elected as Pope Urban VIII, made him archpriest of S. Giovanni in Laterano, and two months later, cardinal deacon of Sant'Onofrio, which was exchanged the following year for Sant'Agata de' Goti.

In 1625, he went to Paris as special legate and from March to September, undertook various negotiations with Cardinal Richelieu[a] including discussions in advance of the Treaty of Monçon.

Overall, the negotiations were not a political success for the papacy but as a ‘sweetener’ he received a gift of six tapestries from King Louis XIII, designed by Peter Paul Rubens.

Pamphili, who took the name of Innocent X (1644–1655) instigated investigation into their handling of the finances in the War of Castro forcing first Antonio to flee to Paris in 1645, to be followed by Francesco and his brother Taddeo Barberini in 1646.

An iconographic programme celebrating the Barberini family, devised by the Tuscan poet Francesco Bracciolini for the vast coved vault of the main salone, was carried out by Pietro da Cortona in an exuberant display of illusionism, colour, movement and ornamentation that marked a new departure for secular Baroque interior decoration.

[15] Also at the Palazzo Barberini, he initiated a small natural science museum and botanical garden and his collections attested to his interests in ancient sculpture, numismatics and inscriptions.

[17] In 1627 Cardinal Barberini was named abbot in commendam of Grottaferrata, and subsequently commissioned Gian Lorenzo Bernini to provide the high altar.

Although initially he made funds available for the construction of San Carlo alle Quattro Fontane designed by Francesco Borromini, these were not sustained.

He also commissioned various monuments for church interiors, including ones to G. Aleandro and B. Guglielmi who had been his teachers, in San Lorenzo fuori le Mura and designed by Cortona.