The company relocated from Bologna to the now historic headquarters on Viale Ciro Menotti in Modena. Ernesto had already designed the 4CL and 8CL engines, which powered the cars of the same name in the late 1930s. The Maserati brothers stayed on in Modena as chief engineers until 1948.

The company dominated the racing scene again, despite strong competition from Mercedes. On 30 May, 1939 it scored an important victory in the Indianapolis 500 with Wilbur Shaw at the wheel of the 8CTF, a feat it repeated the following year. Maserati remains to this day the only Italian marque to have won the Indy 500.

During the Second World War Maserati adapted its production accordingly, turning out machine tools, electrical components, spark plugs and electric vehicles, but returned to its original activities after the war, with a new GT car, the A6 1500.

The A6G CS successfully debuted on the Modena circuit with Alberto Ascari at the wheel; and in those years its racing rivals were the Alfettas, Ferraris and Talbots. After several wins, life became less easy for Maserati in the 1950s as Alfa Romeo and Ferrari were extremely competitive. In 1953 Gioacchino Colombo was appointed Chief Engineer and modified the A6GCM. The team was also strengthened by the arrival of drivers of the calibre of Fangio, Gonzalez, Marimon, Bonetto and de Graffenried and brought home some important victories in the 1953 season; in fact, Fangio won that year's Italian Grand Prix ahead of Ascari’s and Farina’s Ferraris in a race that was only decided after the final corner.

Colombo also laid the foundation for the legendary Maserati 250F, which saw its debut in 1954. Fangio won the Argentine Grand Prix on its debut race.

In 1955 and 1956 Maserati won other important victories; in 1957 Fangio returned to Maserati and won the World Title for the fifth time – the first time for Maserati - with the 250F. Fangio's win in a 250F at the Nürburgring in 1957 is considered by many racing historians to be the greatest drive in the history of the sport.

Although the company announced its official retirement from racing that very year, it never withdrew from the scene completely because Maserati continued to build racing cars like the Birdcage and other prototypes for private teams, and to supply engines for the Formula 1 cars of other constructors, such as Cooper, for which it developed a 12-cylinder, three-valve engine with triple ignition in 1965.

Production of the 3500 GT, which was launched in 1958, began at the start of an important new era for Maserati and consequently the plant had to be expanded. Production cars and sales became the main goals and Maserati’s racing activities became of secondary importance.

The Sebring was presented in 1962 and the Quattroporte in 1963, the first Maserati 4-door saloon with a 90° V8 engine and a displacement of 4,136 cc.