The race was created by the Mexican government in 1950 to celebrate the completion of the 2,178-mile (3,507 km) north-south Mexican section of the Pan-American Highway. Organizers worked closely with the American Automobile Association to promote the event internationally, restricting the inaugural edition to stock sedans with five seats. The first race ran from Ciudad Juarez, Chihuahua, in the north to Ciudad Cuauhtémoc, Chiapas, at the Guatemalan border, comprising nine stages over five days with significant elevation changes ranging from 100 m to 3,195 m above sea level.
The 1950 race was won by American driver Hershel McGriff in an Oldsmobile 88, which proved lighter and easier to stop on the steep, winding course than its larger Lincoln and Cadillac competitors. McGriff completed the course with his original brake shoes intact, a testament to the Oldsmobile's mechanical advantage.
In 1951, the event ran north to south for the first time and attracted works factory entries. Ferrari sent a team including Piero Taruffi and Alberto Ascari, who finished first and second. The race was marred by multiple fatalities, including Mexican aviation pioneer Carlos Panini and competitor José Estrada.
The 1952 edition saw Mercedes-Benz arrive with a highly organized team running the 300 SL (W194). Karl Kling and co-driver Hans Klenk won despite a vulture impacting their windscreen at nearly 200 km/h during the opening stage, briefly rendering Klenk unconscious. Klenk's use of prepared pacenotes to guide Kling through corners proved so effective that the technique was subsequently adopted across all forms of rallying.
The 1953 race was the bloodiest edition. Organized factory efforts from Lancia and Lincoln dominated their respective categories, with Juan Manuel Fangio winning the large sports car class for Lancia and Chuck Stevenson claiming his second consecutive large stock car win for Lincoln. However, Lancia's Felice Bonetto died when he missed his own road markings entering the village of Silao, and six spectators were killed in a separate incident involving Mickey Thompson's car.
The 1954 finale saw Ferrari dominate, with Umberto Maglioli winning at an average speed that was dramatically faster than the inaugural 1950 race. Phil Hill finished second. Seven people died during that edition.
The race was cancelled after the 1955 Le Mans disaster, with the Mexican government citing the completion of the highway's publicity purpose. In total, 27 people died across the five years of the original Carrera Panamericana, giving it one of the highest mortality rates per race in the history of motorsport. Only approximately one-third of entrants typically finished.
The race left a lasting mark on automotive culture. Porsche named several road car models Carrera in honour of their class victories, most notably the 550 Spyder that won the Small Sports Car category in 1953. The watchmaker Heuer introduced a chronograph named the Carrera Panamerica after the 1953 race, which became the long-running Carrera line. Mercedes-AMG introduced a Panamericana grille design, applied to most AMG vehicles from 2018.
The race also served as a rare convergence point for different branches of motorsport. Formula One champions Alberto Ascari and Juan Manuel Fangio competed alongside NASCAR founder Bill France Sr., Indy car drivers Tony Bettenhausen and Walt Faulkner, and hot rod pioneers Mickey Thompson and Ak Miller.
The race was resurrected in 1988 by Pedro Davila, Loyal Truesdale, and Eduardo de Leon Camargo. The modern revival runs a seven-day, approximately 3,100 km route through central Mexico using closed stages on public roads. Entries are organized into ten classes differentiated by car age and bodyshell type. Studebaker Starliner and Starlight coupes from the 1953-54 era, renowned for their aerodynamics and originally designed by Raymond Loewy, have dominated the revival, winning 22 of 29 editions as of 2016. Safety requirements now mandate roll cages, fire suppression systems, HANS devices, and fire-resistant suits; since 2012, maximum stage speeds have been electronically limited to 144 mph.