Lombardi was born in Frugarolo, a small town in the Piedmont region of northern Italy. The youngest of three children, she worked as a delivery driver for her father's butchery business before discovering her passion for motorsport. Her father initially resisted her racing ambitions but came to accept them after she finished runner-up in a 1968 race.
After brief karting experience as a child, Lombardi bought her first car in 1965 and raced it in the Formula Monza series. She competed in Formula Three from 1968 and won the Italian Formula 850 series in 1970. In 1974, she drove a Shellsport-Luxembourg Lola in Formula 5000, finishing fourth.
Lombardi first attempted Formula One in 1974, seeking to qualify with a privately entered Brabham sponsored by Radio Luxembourg — the broadcaster's frequency on 208 metres mediumwave inspired the choice of number 208 as her racing number. The effort was unsuccessful. That winter, Count Vittorio Zanon stepped in as a sponsor, enabling a full 1975 season campaign.
In 1975, Lombardi joined the March team alongside Vittorio Brambilla and Hans-Joachim Stuck, with Zanon's Lavazza Coffee Company providing sponsorship. At the opening race in South Africa, she became the first woman to qualify for a Formula One World Championship Grand Prix since Maria Teresa de Filippis had done so in 1958. The season's defining moment came at the Spanish Grand Prix, where Lombardi ran to sixth place before retiring with a fuel system problem. The race was halted after 23 laps following a catastrophic accident involving Rolf Stommelen's car, which killed four spectators. Because the race was stopped before three-fifths of the scheduled distance was complete, all points were halved — giving Lombardi half a point, the only world championship point any woman has ever scored. She also finished seventh at the German Grand Prix at the Nürburgring that year, and ran a one-off for Williams at the United States Grand Prix, though an ignition problem prevented her from starting.
For 1976, Lombardi was confirmed at March alongside Brambilla and Stuck again but was replaced after the Brazilian Grand Prix. She moved briefly to RAM Racing, recording a best finish of 12th at the Austrian Grand Prix. Her total Formula One World Championship career spanned 17 starts between 1974 and 1976.
In 1974, Lombardi was the first female driver to qualify and compete in the Race of Champions at Brands Hatch, finishing 14th in a Lola-Chevrolet. She returned and qualified for the 1975 event as well, retiring after 20 laps.
After Formula One, Lombardi built a substantial sportscar career in European endurance racing. 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 being 20th overall and second in the GTP class in 1976 sharing a Lancia Stratos Turbo. Further podium finishes included third at Casale in 1974, third at the Imola 250 km in 1977, and second at multiple events in 1979 and 1981.
Lombardi also competed in the 1977 Firecracker 400 NASCAR race at Daytona International Speedway, finishing 31st alongside two other female drivers: Janet Guthrie and Christine Beckers.
She retired from racing in 1988, and in 1989 founded her own team, Lombardi Autosport.
Lombardi died of breast cancer in Milan on 3 March 1992, aged 50. She was buried in her hometown of Frugarolo, where she is commemorated by a sculpture. Lombardi was one of the first prominent female racing drivers known to have been openly in a same-sex relationship.
Her achievements have shaped how women are perceived in motorsport. She and Maria Teresa de Filippis remain the only two women to have started a Formula One World Championship Grand Prix, and Lombardi alone ever scored points in one. Subsequent generations of female drivers — in roles ranging from test and development drivers to race engineers and strategists — are frequently cited as following a path that Lombardi helped open. A 2020 documentary film, "Beyond Driven," chronicled her life and impact.