Known since the early 15th century, the family received a confirmation of nobility from the Holy Roman Emperor in 1563.

In the 18th century, the naval officer Franz Fesch (1711–1775) entered the service of the Republic of Genoa and established a branch in Corsica.

The goldsmith and member of the city council Hans Rudolf Faesch (1510–1564) was ennobled by Ferdinand I, Holy Roman Emperor in 1563 and received a confirmation of the family arms that added two stars to their crest.

Thus the family held a dual status as patricians or members of the Daig of the burgher republic of Basel, and as nobles of the Holy Roman Empire.

The diplomat Johann Rudolph Faesch (1669–1751) was an adviser to the Margrave of Baden, representative of the Elector of Trier and the Duke of Württemberg at the Court of France.

Their son Joseph Fesch (born 1763 in Ajaccio, died 1839 in Rome) was the half-brother of Letizia Ramolino (a daughter of Angela Maria's first marriage) and through his sister the uncle of Napoleon Bonaparte.

Joseph Fesch became Archbishop of Lyon in 1802, was named a Cardinal in 1803, became French Ambassador to Rome in 1804, became a French senator and count in 1805, became Grand Almoner of France in 1805, obtained the rank of a sovereign prince with the style of Most Eminent Highness as he was chosen as coadjutor of the Prince-Bishopric of Regensburg in 1806, was named a French Prince (prince français) with the style of Serene Highness in 1807, received the Great Eagle (the highest degree) of the Legion of Honour, was a Knight of the Order of the Golden Spur (1802), a Knight of the Order of the Golden Fleece (1805), became a Peer of France in 1815 and subsequently[when?]

Cardinal Fesch lived out his days at the Palazzo Falconieri in Rome, dedicating himself to art and to beneficence.