There was a two-month break after the French GP before the final round of the World Championship at Monza. In that time the Alfa Romeo domination had continued in non-championship races at Bari, Geneva, Pescara and in the International Trophy at Silverstone. The Ferraris had been beaten in Holland by Talbot Lago and then Luigi Villoresi suffered serious injuries in Geneva and so was out of action for the Italian GP. The new 4.5-liter Ferrari 375 appeared in the hands of Dorino Serafini and Alberto Ascari. The Alfas as usual were driven by Giuseppe Farina, Juan Manuel Fangio and Luigi Fagioli although there were two other 158s for Piero Taruffi and Consalvo Sanesi. The rest of the field was made up of the usual Talbot Lagos and Maseratis although the factory Talbot team was not there. There were a couple of Simca-Gordinis for Maurice Trintignant and Robert Manzon and a curious Ferrari-Jaguar driven by Clemente Biondetti.

Practice saw Fangio beating Ascari's Ferrari with the front row completed by Farina and an impressive Sanesi. The second row of the 4-4-4 grid featured Fagioli, Serafini, Taruffi and Raymond Sommer in the first Talbot Lago. Although eighth on the grid he was 10secs a lap slower than Fangio.

The race saw the first serious challenge to Alfa Romeo in a World Championship event with Ascari battling with Fangio and Farina. After 21 laps Ascari retired with an overheating engine and Fangio went out soon afterwards with a gearbox problem. He later took over Taruffi's car but this also retired. Ascari took over Serafini's Ferrari and managed to take second place ahead of Fagioli. The World Championship ended with victory for Farina, three points clear of Fangio.