Born in Comunanza, in the Marche (then part of the Papal States), he was the son of the painter Sebastiano Ghezzi, a painter and architect for the papacy of Pope Urban VIII. Sebastiano died when Giuseppe was only 11 years old, and he was sent to Fermo to study philosophy an letters, but took also painting instruction under Lorenzino da Fermo. He then moved to Rome where he chose painting over law studies. He painted in many Roman churches.
He painted in the style of Pietro da Cortona. Giuseppe Ghezzi was the first secretary in perpetuity for the Accademia di San Luca in Rome. He was the father of the more prominent caricaturist Pier Leone Ghezzi (born June 28, 1674). Another son, Placido, was Apostolic Protonotary. Giuseppe was also a mentor to Pietro da Pietri (1634–1721).
On December 10, 1676, he borrowed a number of privately owned works by Venetian masters and exhibited them in the cloisters of San Salvatore in Lauro in Rome. He published a book of collected poems about art that describes an academic competition.
- Ricci, Amico (1855). Memorie storiche delle arti e degli artisti della marca di Ancona Volume 1.
- Sebastiano was a pupil of Guercino.
- Biografia universale antica e moderna ossia Storia per alfabeto della vita; Volume 24, Presso Giovanni Battista Missiaglia, Tipografia di Alvisopoli, entry by Dizionario Storico di Bassano, page 160.
- A. Ricci page 328
- Ghezzi, Giuseppe (1726). Le Tre Belle Arti Pittura , Scultura, e Architectura, In Lega coll'Armi per difesa della Religione:Mostrate nel Campidoglio Sall'Accademia del Disegno, Reggendo il Principato della medesima il Cavalier Carlo Francesco Person.. Rome: Stamperia di Giovanni Maria Salvioni nell'Archiginnasio della Sapienza. pp. 72–73.
- Memorie intorno i letterati e gli artisti della città di Ascoli nel Piceno, by Giacinto Cantalamessa Carboni, Page 215.
- Farquhar, Maria (1855). Ralph Nicholson Wornum, ed. Biographical catalogue of the principal Italian painters. London; Digitized by Googlebooks from Oxford University copy on Jun 27, 2006: Woodfall & Kinder. pp. 72–73.