For the 1952 season, following Alfa Romeo's withdrawal from Formula One, the FIA announced that rounds counting toward the World Championship of Drivers would be held to Formula Two rather than Formula One rules. Ferrari was uniquely positioned as the only team to have built a car specifically designed for the new formula. The 500 was powered by an inline four-cylinder engine mounted behind the front axle, improving weight distribution relative to its predecessors.
Alberto Ascari drove the Ferrari 500 to win his first World Championship in 1952, claiming victory in all but one round. His sole absence was due to his participation in the Indianapolis 500, where Ferrari entered a larger 4.5-litre car. Remarkably, Ferrari won that race too in Ascari's absence. The combination of the 500's purposeful design and Ascari's skill produced a level of dominance seldom seen in championship racing.
The 1953 season saw Ferrari and Ascari repeat the achievement. Ascari won his second consecutive World Championship, and Ferrari took all but the final race of the season, which was won by Juan Manuel Fangio — returning to competition after an accident had kept him away from the sport. Ascari's run of seven consecutive World Championship race victories in the Ferrari 500 stood as a record until Sebastian Vettel surpassed it in 2013. When the 1953 Indianapolis 500 — run to a different formula — is excluded from the count, the sequence of victories extends to nine.
When the World Championship returned to Formula One engine regulations for 1954, Ferrari 500 chassis were modified to accept the new 2.5-litre 625 engine. In this guise the car was known as the Ferrari 625 F1. The 625 engine displaced 2498.32 cc and produced between 210 and 230 PS at 7000 rpm, fed by two Weber 50DCO carburettors. Suspension consisted of an independent front end and a de Dion rear axle, with transverse leaf springs and Houdaille hydraulic dampers at both ends.
The 625 F1 won two further World Championship races, one in 1954 and one in 1955, though it was not fully competitive against the Mercedes-Benz W196 or the Maserati 250F. In May 1955, Maurice Trintignant drove the 625 to win the Monaco Grand Prix. The car remained in use until 1956, when Ferrari adopted the Lancia D50 chassis acquired along with Lancia's Formula One team.
The Ferrari 500's run of two consecutive championship-winning seasons, during which it was effectively unbeatable, remains one of the most complete acts of domination in the sport's history. Ascari's nine-race winning streak — the longest in the championship at the time — reflected both the soundness of Lampredi's design and the coherence of Ferrari's engineering programme during that era.