Born in Rome, Musso started his career in sportscar racing before progressing to Formula One in 1953 with Maserati at the Italian Grand Prix.

Musso raced full-time for Maserati in 1955, repeating his podium feat at the Dutch Grand Prix.

On debut for Ferrari, Musso won the Argentine Grand Prix alongside Juan Manuel Fangio,[a] completing 30 of the 98 laps, but his season was curtailed after a sportscar crash at the Nürburgring.

During his time at Ferrari, Musso entered into a fierce rivalry with British drivers Mike Hawthorn and Peter Collins.

During the 1958 French Grand Prix at Reims, Musso died whilst chasing Hawthorn, when his Ferrari 246 went airborne and critically injured him.

He shared victory in the 1956 Argentine Grand Prix with Juan Manuel Fangio, however his season was cut short after a crash in a sports car race at Nürburgring.

Musso triumphed in a Ferrari 290 MM in the City of Buenos Aires sports car race on 20 January 1957.

Later in the year he shared a 4-litre modified Formula One Ferrari 412 MI with Phil Hill and Mike Hawthorn in the 2nd Race of Two Worlds on the Monza banked oval.

Breschi related that at the time of his death, Musso was in debt, and thus winning the French Grand Prix (traditionally the largest monetary prize of the season) was all-important to him.