Development of the 450S began in 1954 under engineers Vittorio Bellentani and Guido Taddeucci, who sought to equip Maserati with a larger-displacement car than the company had previously fielded. The original project, codenamed Tipo 54, was shelved in 1955 following the catastrophic Le Mans disaster that year. It was revived in early 1956 when American housing developer Tony Parravano commissioned Maserati to build a large-bore V8 engine for a Kurtis Indy chassis, prompting the factory to resurrect and refine the Tipo 54 concept.
The engine was a short-stroke V8 of 4,477 cc with a 93.8 mm bore and 81 mm stroke, four 45 IDM Weber carburetors mounted within the vee, and double overhead camshafts. Output was rated at 400 hp at 7,200 rpm. The chassis, designed by Valerio Colotti, used a tubular frame derived from the Maserati 350S but elongated to accommodate the V8. Front suspension employed double wishbones and coil springs, while the rear used a heavily reinforced de Dion axle paired with a new five-speed transaxle mounted ahead of the de Dion tube — an unusual arrangement that extended the gearbox section forward of the final drive. Drum brakes borrowed from the 300S were retained with improved cooling. Medardo Fantuzzi designed the open bodywork, which bore a family resemblance to the 300S.
The prototype made its competitive debut at the 1956 Swedish Grand Prix, renumbered 4501. Despite impressive raw pace, the car suffered from a chassis unable to cope with the V8's power output and an incorrect firing order that produced severe vibration. It qualified third but was withdrawn and returned to the factory, where a purpose-built replacement chassis was constructed.
For the 1957 season, the 450S became Maserati's frontline weapon in the World Sports Car Championship. At the Buenos Aires 1,000 km, chassis 4501 was driven by Stirling Moss and Juan Manuel Fangio, only for a clutch failure to prevent what had looked like a certain victory from an early dominant position. Chassis 4503, driven by Fangio and Jean Behra, won the 12 Hours of Sebring — the 450S's most celebrated result. That same chassis later won the Swedish Sports Car Grand Prix in the hands of Behra and Moss, though it was also twice crashed by Behra during the Mille Miglia practice and at Le Mans.
The Le Mans entry of 4501 took a distinctive form: Frank Costin of England designed a coupé body built by Zagato, aimed at improving aerodynamics for the Mulsanne Straight, but fundamental design flaws meant the car failed to finish.
Chassis 4505, shared by Moss and journalist Denis Jenkinson, retired from the Mille Miglia when the brake pedal fell off, and subsequently suffered a wheel departure at the Nürburgring 1,000 km. Chassis 4507, entered in Venezuela, was destroyed in a fiery crash alongside 4503 during the final round of the 1957 championship, inflicting severe financial damage on Maserati.
Maserati ended the 1957 World Sports Car Championship as runner-up to Ferrari, accumulating 25 points to Ferrari's winning total of 30. Victories at Sebring and the Kristianstad race in Sweden, combined with supporting results from the sister 300S, were not enough to overturn Ferrari's wins at Buenos Aires, the Mille Miglia, and Venezuela.
The destruction of multiple cars in Venezuela — caused by the simultaneous crashes of 4503 and 4507 — proved financially ruinous and forced Maserati to withdraw from factory racing entirely at the end of 1957. The 450S's career effectively ended with the introduction of a 3-litre displacement limit for the World Sports Car Championship, which rendered the large V8 obsolete.
Several chassis were sold to American privateers, with some fitted with enlarged engines of 5.7 and 6.6 litres for SCCA competition. Drivers including Carroll Shelby, Jim Hall, Masten Gregory, Walt Cline, and Ebb Rose raced these cars in the United States.
Between 1956 and 1962, the 450S made 119 appearances and claimed 31 victories, testament to the car's speed even if unreliability and misfortune prevented a championship title.
The 450S stands as one of the most powerful and dramatic sports cars of the 1950s, matching Ferrari's 315 S and 335 S and outpacing the Jaguar D-Type and Aston Martin DBR1 in outright speed if not reliability. The type's influence persisted in automotive culture: in 2015, Zagato presented the Maserati Mostro concept at the Concorso d'Eleganza Villa d'Este, a modern tribute to the original Costin-Zagato coupé body fitted to chassis 4501.