Lombardi was born in Frugarolo, a small town in Piedmont, on 26 March 1941, the youngest of three children. Her father was a butcher and gave her her first driving job as a delivery driver for the family's shop. He was initially resistant to her passion for racing but became supportive after she finished runner-up in a 1968 event.
After a brief introduction to karting as a child, Lombardi bought her first racing car in 1965 and competed in the Formula Monza series. She progressed to Formula Three in 1968 and won the Italian Formula 850 series in 1970. In 1974, she drove in Formula 5000 with the Shellsport-Luxembourg Lola, finishing fourth. Her performances attracted sponsorship and, eventually, a Formula One opportunity.
Lombardi's first attempt to qualify for Formula One in 1974, using a privately entered Brabham supported by the Automobile Club d'Italia and sponsored by Radio Luxembourg, was unsuccessful. That winter she met Italian nobleman Count Vittorio Zanon, whose sponsorship — via the Lavazza coffee company — enabled her 1975 Formula One campaign with March Engineering, alongside Vittorio Brambilla and Hans-Joachim Stuck.
At the opening race of 1975 in South Africa, Lombardi became the first woman since Maria Teresa de Filippis in 1958 to successfully qualify for a Formula One World Championship Grand Prix. The season's defining moment came at the Spanish Grand Prix at Montjuich Park in Barcelona. With 23 laps completed, the rear wing of Rolf Stommelen's Hill GH1 failed at speed, sending his car into the crowd and killing four spectators. The race was stopped after a further four laps. At the point of stoppage, Lombardi was sixth. Because the race had not reached three-fifths of its scheduled distance, all points were halved; Lombardi was credited with half a point — still the only championship points ever scored by a female Formula One driver.
Lombardi also impressed at the German Grand Prix at the Nürburgring that year, finishing seventh. At the United States Grand Prix at Watkins Glen she took a one-off drive for Williams but was prevented from starting due to an ignition problem.
For 1976, Lombardi was confirmed at March alongside Brambilla and Stuck. She finished 14th at the Brazilian Grand Prix before the team replaced her with Ronnie Peterson. She subsequently drove for RAM Racing, with her best result being 12th at the Austrian Grand Prix. After 1976 her Formula One programme concluded.
In 1974, Lombardi was the first female racing driver to qualify and compete in the Race of Champions at Brands Hatch, racing a Lola-Chevrolet Grand Touring Prototype. She finished 14th. She returned in 1975 with a March-Ford entry, retiring after 20 laps.
Lombardi found sustained success in sports car racing after her Formula One programme ended. In 1979 she won the 6 Hours of Pergusa and the 6 Hours of Vallelunga; in 1981 she won the 6 Hours of Mugello. She competed four times at the 24 Hours of Le Mans, with her best result coming in 1976 when she finished 20th overall and second in the GTP class in a Lancia Stratos Turbo. She also collected podium finishes at Casale in 1974, Imola in 1977, Wunstorf and Ulm in 1979, and Monza and Donington in 1981. In 1977, Lombardi competed in the Firecracker 400 NASCAR race at the Daytona International Speedway, finishing 31st in a field that also included American Janet Guthrie and Belgian Christine Beckers.
Lombardi retired from racing in 1988 and in 1989 founded Lombardi Autosport, her own racing team.
Lombardi was one of the first female racing drivers openly in a same-sex relationship. She died of breast cancer in Milan on 3 March 1992, aged 50, and was buried in her home town of Frugarolo, where a sculpture now commemorates her. She was survived by her partner, Fiorenza.
Lombardi's Formula One career — culminating in that solitary half-point at the 1975 Spanish Grand Prix — remains a landmark in the sport's history. She and Maria Teresa de Filippis are the only two women to have started in Formula One World Championship Grands Prix, and Lombardi remains the only woman to have finished in the points. Her career influenced subsequent generations' perceptions of women in motorsport, and she is widely cited as a trailblazer whose achievements extended well beyond the numerical record. A 2020 biographical film, Beyond Driven, documented her life and racing career.