Enzo Coloni, a native of Perugia who competed in Italian Formula Three and European Formula Two in the late 1970s, founded the team in 1982 and retired from driving the following year to focus on management. The team's logo featured a wolf — a nod to Enzo's aggressive racing style, which had earned him the nickname "Il Lupo" (the wolf).
Coloni's initial period in Italian Formula Three was highly successful. The team secured the drivers' championship for three consecutive years: Enzo Coloni himself in 1982, Ivan Capelli in 1983, and Alessandro Santin in 1984. Nicola Larini repeated the achievement in 1986, and in that same season, Larini and Gabriele Tarquini competed in Formula 3000 with a March 85B, Tarquini finishing tenth in the championship.
Sensing opportunity when the FIA announced that turbo engines would be banned from 1989, Enzo Coloni moved the team into Formula One at the 1987 Italian Grand Prix. The team spent five seasons in the top category using Ford-Cosworth power, with Gabriele Tarquini achieving the team's best result — eighth place at the 1988 Canadian Grand Prix — in a largely undistinguished period.
A 1990 partnership with Subaru proved ill-fated: the flat-12 engine designed by Carlo Chiti produced insufficient power, was installed in the car for the first time in a Phoenix supermarket parking lot, and failed to qualify for a single race all season. Despite Subaru withdrawing mid-year and returning the team debt-free to Enzo Coloni, the experiment left the team without direction. The 1991 season, using an updated 1989 chassis with only six team members, was the team's final Formula One campaign. Enzo Coloni subsequently sold the operation to Andrea Sassetti, who rebranded it as Andrea Moda Formula for 1992.
The Coloni name remained active in Italian Formula Three through the 1990s under Paolo Coloni's management, fielding drivers including Esteban Tuero and Dino Morelli. The team stepped up to International Formula 3000 in 1997.
Coloni Motorsport reached its F3000 zenith in 2002, when Giorgio Pantano and Enrico Toccacelo shared driving duties. Pantano finished as series runner-up, with Toccacelo ninth, the pair combining for three race wins. The following year, Ricardo Sperafico again finished as runner-up, while Zsolt Baumgartner — who also made his Formula One debut for Jordan at the Hungarian Grand Prix — drove the second Coloni entry.
Coloni carried its Formula 3000 entry into the GP2 Series when the championship was rebranded in 2005. Mathias Lauda and Gianmaria Bruni — the latter fresh from a Minardi Formula One season — opened the team's GP2 account, though Bruni departed before the final three rounds.
At the end of 2005, Formula One driver Giancarlo Fisichella partnered with the Coloni operation, and from 2006 to 2009 the team competed as Fisichella Motor Sport.
The team reappeared under the Coloni name for 2010, running Brazilian Alberto Valerio alongside Bulgarian Vladimir Arabadzhiev, with Brendon Hartley taking over Arabadzhiev's seat for the final two rounds. The team scored 18 points and finished tenth in the Teams' Championship.
In 2011, Coloni started with Michael Herck and Davide Rigon. Rigon suffered multiple fibula fractures in a first-race collision in Istanbul and was replaced by 17-year-old Kevin Ceccon. Halfway through the year the team had gathered just one point. The situation changed dramatically when veteran Luca Filippi joined for the Nürburgring round: he won the Feature Race on his debut, added wins at Spa-Francorchamps and Monza, and finished runner-up in the championship to Romain Grosjean with 44 points. Herck finished 21st; Coloni ended the season seventh in the teams' standings.
At Silverstone in 2012, the series organisers and the team announced that Coloni would leave the GP2 Series before the season's end, forfeiting all points accumulated. No explanation was provided for the abrupt exit.
Paolo Coloni Racing entered the Auto GP series in 2015, continuing the family's involvement in junior single-seater racing.