The final championship round of the season was the Italian Grand Prix at the Monza Autodrome near Milan, and all three of the regular Alfa Romeo drivers were in contention for the title. If Fangio finished first or second, he would win the title, regardless of where his teammates finished. If Farina failed to score at least five points, he would be unable to take the title. Fagioli's only chance of becoming World Champion was if he won the race and set the fastest lap; even then, he would need Farina to finish no higher than third, and Fangio would have to score no points at all.

Fangio again took pole position, but Alfa Romeo could not make it a fifth front-row lockout of the season, as Ascari qualified second for Ferrari. Farina started from third, while Consalvo Sanesi completed the front row in an additional Alfa Romeo. Fagioli could only manage fifth on the grid, alongside the fifth Alfa of Piero Taruffi, the second Ferrari of Dorino Serafini, and Sommer in a Talbot-Lago. Farina took the lead early on, with Ascari and Fangio not far behind. Ascari briefly held the lead but was forced to retire when his engine overheated. Two laps later, Fangio also retired due to problems with his gearbox. Taruffi's car, which was now running in second, was taken over by Fangio, although the Argentinian was forced to retire for the second time in the race, this time with engine problems. Ascari took over Serafini's car and ultimately finished second behind Farina, whose victory clinched the title by taking him three points clear of Fangio. Fagioli finished third in the race, and clinched the same position in the Drivers' Championship standings.