Patrese grew up near the Italian Alps and was selected for the national ski team as a teenager, also competing in swimming. He won the Karting World Championship in 1974 at Estoril. After Formula Italia in 1975, he dominated Formula Three in 1976, winning both the Italian and European championships. He graduated to Formula Two in 1977 before making his Formula One debut mid-season with Shadow.
Patrese debuted at the 1977 Monaco Grand Prix with Shadow, scoring his first championship point in Japan later that year. He joined the newly formed Arrows team in 1978 alongside Rolf Stommelen after team leader Jackie Oliver departed Shadow. In Arrows' second race, the South African Grand Prix, Patrese led until engine failure struck fifteen laps from the end.
His reputation suffered gravely at the 1978 Italian Grand Prix at Monza, where a first-lap accident involved ten cars. Ronnie Peterson, who sustained leg injuries in the incident, died from an embolism the following day. Several leading drivers — including James Hunt, Niki Lauda, Mario Andretti, Emerson Fittipaldi, and Jody Scheckter — declared they would withdraw from the next race unless Patrese was banned. The organizers agreed. Patrese was later acquitted of manslaughter charges in an Italian court on 28 October 1981, but the stigma from Peterson's death followed him throughout his career, with Hunt regularly criticising him during BBC commentary.
Despite this background, Patrese delivered strong performances at Long Beach, finishing second in 1980 and taking pole in 1981 before a fuel filter failure retired him from the lead.
Patrese moved to Brabham in 1982 and claimed his maiden Formula One win at Monaco in extraordinary circumstances. He had inherited the lead when Alain Prost crashed, but then spun on the damp track. Cars behind him pitted or retired on the final lap — Didier Pironi with an electrical fault, Andrea de Cesaris out of fuel — handing Patrese the win. He added a second victory at the 1983 South African Grand Prix. The period at Brabham was followed by two unrewarding seasons at Alfa Romeo, where fuel consumption restrictions regularly negated competitive race positions.
Patrese's career was revived when Williams drafted him in as a substitute for the injured Nigel Mansell at the 1987 Japanese Grand Prix. A half-second faster than Senna's pole time in a private Imola test convinced the team to sign him for the 1988 season alongside Mansell. After difficult years with the Judd-engined car in 1988, the arrival of Renault V10 power in 1989 returned Patrese to genuine competitiveness. He finished third in the championship that year, took four second-place results, and led the opening race in Brazil before a radiator failure.
In 1990 he won his third career Grand Prix at the San Marino race at Imola. A further two victories in Mexico and Portugal in 1991 gave Patrese his best individual season. He out-qualified Mansell at every race until the halfway point and contributed materially to the Englishman's championship campaign, offering consistent points in close partnership. He finished third in the championship behind Mansell and Ayrton Senna.
The 1992 season brought the most dominant car of his career, the Williams FW14B, but also the most frustrating dynamic. He was asked to move aside for Mansell while leading the French Grand Prix and diplomatically deflected all questions about team orders with a repeated "no comment." He took one win at the Japanese Grand Prix and finished runner-up in the championship to Mansell, his best ever final standing.
After six years at Williams, Patrese signed with Benetton for 1993 to partner Michael Schumacher. He found the team's attention focused entirely on Schumacher and the car a step down from the Williams he had left. He scored twenty points and his final podium — a second at the Hungarian Grand Prix. Flavio Briatore informed him he was free to find another drive before the season ended. Patrese chose retirement rather than accept what he considered a further downgrade with Ligier.
Patrese's 256 starts set a record that stood from 1993 until 2008. His six wins were spread across an extraordinary span: there was a gap of more than six years between the 1983 South African Grand Prix and the 1990 San Marino Grand Prix, the longest interval between two wins in the modern era. His career illustrated remarkable longevity in a sport where most drivers peak sharply then fade; he was thirty-eight when he finished second in the 1992 championship. After retiring from Formula One he took up show jumping, winning an Italian national amateur title before stepping back from equestrianism in 2014.