[3] Throughout the 1630s, Donghi was employed in a number of administrative positions in Rome including referendary of the Tribunals of the Apostolic Signature of Justice and of Grace.

[4] Donghi was created a cardinal-deacon by Pope Urban VIII in the consistory of 13 July 1643, and assigned the Deaconry of San Giorgio in Velabro on 31 August 1644.

[7] Urban died a year later, on 29 July 1644, and Donghi was one of the fifty-seven cardinals[8] who participated in the papal conclave of 1644.

On 3 July 1651 Cardinal Donghi was named Legatus in the Romandiola and the Exarchate of Ravenna by Pope Innocent X.

[11] An inscription in Ravenna, dated 1654, commemorates Donghi's providing supplies of grain to the city during a famine.

[18] On 26 February 1663, Cardinal Donghi was released from his commitment to Imola, and appointed bishop of Ferrara; he held the diocese until his death.

Cardinal Giovanni Stefano Donghi died on 26 November 1669[21] and was buried in the Chapel of the Madonna at the Church of the Gesù in Rome.