Founded in Milan, Italy, in 1900 by Cesare Isotta and the brothers Vincenzo, Antonio, and Oreste Fraschini, in 1955 it was merged with engine manufacturer Breda Motori and renamed F.A.

The firm was named for its founders, Cesare Isotta and Vincenzo Fraschini, who had been importing Mors and Renault automobiles as well as Aster proprietary engines since 1899.

The firm started making race cars using this same 100 horsepower (75 kW) engine, establishing the company's reputation and giving its name considerable cachet.

[4] Isotta Fraschini introduced their Tipo 8, the first production automobile to be powered by a straight-eight engine, at the Paris Salon in 1919[5] and began delivering them to customers in 1920.

Also, an Isotta Fraschini was gigolo Lindsay Marriott's car in Raymond Chandler's book Farewell, My Lovely (1940) that was made into the motion picture Murder, My Sweet (1944), starring Dick Powell and Claire Trevor.

Isotta Fraschini had initially planned for a 2023 debut of the Tipo 6 LMH-C in the FIA World Endurance Championship at the 6 Hours of Spa, partnering with the British team Vector Sport.

[15][16] In its inaugural season in the World Endurance Championship, the car was driven by Carl Bennett, Antonio Serravalle, and 2013 24 Hours of Le Mans Pro-Am winner Jean-Karl Vernay.

[17] The brand competed in five races, and finished only three, before withdrawing from the 2024 World Endurance Championship season prior to the 2024 Lone Star Le Mans due to disputes with Duqueine Team.