Racing at Pergusa began in the 1960s when the track hosted sportscar events including the Coppa Citta di Enna, which received rounds of the World Sportscar Championship between 1962 and 1967. During the 1970s the venue hosted the Coppa Florio, one of the oldest names in motorsport, revived as a sports car race from 1974 onwards. The Coppa Florio at Pergusa counted towards the World Sportscar Championship for most years between 1975 and 1981.
The circuit also held a non-championship Formula One event, the Mediterranean Grand Prix, during the 1960s and 1970s under European Formula Two regulations. The race ran from 1967 to 1984 in various forms, providing a platform for Formula Two and Formula Three racing during that period.
In 1989 the Italian round of the Superbike World Championship was held at Pergusa, marking its most prominent international motorcycle event. Through the 1990s the track was upgraded and began attracting higher-category international series, hosting rounds of the FIA Sportscar Championship and FIA GT Championship. The International Formula 3000 series visited Pergusa regularly from 1985 to 1998 under the Mediterranean Grand Prix banner and then under Euro Formula 3000 from 1999 to 2003. The 1997 Ferrari Festival was also staged at the circuit.
The European Touring Car Championship and its successor series returned repeatedly, with rounds held across multiple decades. The European Touring Car Cup visited the circuit in 2013, 2014, and 2015.
The Autodromo di Pergusa developed a particular reputation for difficult conditions. The proximity of the lake meant the circuit surface accumulated dust and became abrasive, making it notably slippery and hard on tyres. Formula 3000 events at the venue were also criticised for poor organisation and marshalling standards, reflecting the challenges of operating a significant international event in a remote inland Sicilian location.
In 2020 Creventic hosted a 12-hour race at Pergusa as part of the 24H GT Series, simultaneously reviving the Coppa Florio name for the event, held across two days in October. This represented a return of endurance racing to the circuit after a long gap. The Italian GT Championship continued to use the venue into the 2020s, with rounds in 2021, 2022, and 2023 keeping the circuit active in national-level competition.
Pergusa occupies an unusual place in Italian motorsport history: it is not a purpose-built purpose-only venue in the way of Monza or Imola, but rather a track defined by its natural surroundings, with the lake at its centre forming an integral part of the circuit's identity. Its long history of hosting international series across multiple categories — from World Sportscar Championship rounds in the 1960s and 1970s through Superbike and GT racing — gives it a heritage disproportionate to its modest profile outside Italy.