Mantz built his racing career across multiple disciplines, competing in open-wheel championship cars, endurance road races, and stock cars. His varied career reflected the fluidity of American racing during the postwar period, when drivers commonly crossed between series and formats.
Mantz made 17 starts in the AAA Championship Car series between 1948 and 1952. In his debut season, he captured a victory at the Milwaukee Mile, as well as winning the non-championship Indianapolis Sweepstakes at Williams Grove Speedway. He made two Indianapolis 500 appearances. In 1948, starting eighth, he was black-flagged and finished a classified 13th after completing 185 laps. The following year he started ninth and ran all 200 laps to finish seventh. In 1953, Mantz participated in the Indianapolis 500 in a relief role, driving for Walt Faulkner. Because the 1950–1960 Indianapolis 500s counted toward the FIA World Championship, this relief appearance gave Mantz a credited World Championship start, though he scored no points.
Mantz competed as a member of the Lincoln factory team in the inaugural Carrera Panamericana in Mexico in 1950. He and co-driver Bill Stroppe led significant portions of the grueling multi-day road race. However, approaching the finish line with no remaining spare tires, Mantz was forced to run on bare wheel rims over the final stretch and ultimately crossed the finish line ninth.
Mantz's most celebrated moment in motorsport came at Darlington Raceway in South Carolina on September 4, 1950, when he won the inaugural Southern 500. The race was notable on multiple fronts: it was the first 500-mile race ever held in NASCAR, Darlington was the sport's first superspeedway (measuring just under a mile and a half), and it was the only paved event on the 1950 NASCAR calendar.
Mantz and his Plymouth had been the slowest qualifiers, nearly ten miles per hour slower than pole-winner Curtis Turner, and he started 43rd in a 75-car field. His race strategy, however, proved decisive. Mantz fitted his Plymouth with truck tires that were more durable and resistant to wear than conventional racing tires. While competitors repeatedly pitted for tire changes on the harsh new pavement, Mantz ran long and steady, winning by nine laps over second-place finisher Fireball Roberts. His average speed was 75.250 mph, and the race took more than six hours to complete. The car carried a single sponsorship decal for Justice Brothers, a product distributor. Darlington Raceway continues to present the Johnny Mantz trophy to the winner of the Southern 500 in his honor.
Mantz went on to become the first USAC Stock Car national champion in 1956. He made 12 NASCAR Grand National starts between 1950 and 1956 and was also the first person to attempt to bring NASCAR-sanctioned racing to the West Coast of the United States. His final stock car race was in Pomona, California in 1958, which he won.
Mantz appeared in several Ford automobile magazine advertisements in the early 1960s. He died on October 25, 1972, aged 54, in a fatal car accident near Ojai, California.
Mantz occupies a unique place in NASCAR history as the winner of the first 500-mile race in the sport's history. His 1950 Southern 500 victory — achieved against overwhelming odds as the slowest qualifier in a large field — demonstrated the importance of tire strategy and mechanical preparation at a time when the sport was establishing its identity. The trophy bearing his name at Darlington keeps that legacy visible for each subsequent generation of Southern 500 competitors.