MV Agusta's three-cylinder machine, the Tre, had carried Giacomo Agostini to the world championship every year from 1966 to 1972. By the 1972 season, the Tre was barely capable of holding off the improving two-stroke competition from Yamaha and Suzuki. For 1973, MV engineers bored an existing 350 cc four-cylinder engine out to 433 cc — an engine capable of higher revs than the Tre — producing 88 bhp at 14,000 rpm. Chief engineer and race director Arturo Magni found reliability elusive with the smaller, lighter unit, and Agusta's helicopter division was brought in under Dr. Bocchi, who had previously worked on twelve-cylinder engines for Lamborghini and Ferrari.
The finished engine displaced 497 cc, with a bore of 58 mm and stroke of 47 mm. Its single-piece cast cylinder head used pent-roof combustion chambers with two inlet valves of 20.5 mm and two outlet valves of 16 mm, operated by bucket tappets. Camshaft drive was via gears arranged between cylinders 2 and 3. The unit weighed 55 kg dry and measured 40 cm in width.
The four-cylinder's debut season was complicated by the arrival of Phil Read as a second factory rider alongside Agostini, a pairing that generated immediate internal tension. The machine was unreliable early in the year, requiring frequent use of the older Tre. Jarno Saarinen's Yamaha TZ 500 dominated the opening rounds before a fatal accident at Monza killed Saarinen and Renzo Pasolini, prompting Yamaha's withdrawal from the remainder of the season. Read capitalised to win the championship, becoming world champion at the Swedish Grand Prix.
Agostini's departure to Yamaha — motivated by dissatisfaction at sharing the team with Read — brought Gianfranco Bonera into the squad. The four-cylinder had matured into a substantially stronger machine, but competition had intensified sharply, with Yamaha's YZR 500 factory racer, production TZ 500s, and the new Suzuki RG 500 all on the grid. Handling remained a concern; chassis modifications throughout the year included a central rear suspension and new Ceriani forks. Read clinched his second consecutive world title with victory at the Finnish Grand Prix, and Bonera took second overall in the final standings.
Read entered the season dissatisfied with the four-cylinder's handling, leading to a switch to a tubular frame in place of the original double-loop structure. Bonera broke a leg in pre-season testing and was replaced by Armando Toracca. Agostini, now on a Yamaha, proved the dominant force. Read won in Belgium and took second in Sweden but retired in Finland, leaving the title contest open heading to Czechoslovakia. When Agostini made a fuel stop and Read won the race, Agostini's second place nonetheless secured his seventh 500 cc championship — and the first won on a two-stroke in the class.
Agostini returned to MV Agusta for 1976 after Yamaha's official withdrawal from racing, while Read moved to Suzuki. The machines were delivered to the Marlboro-Api Racing Team, though factory engineers remained in attendance. New FIM noise regulations limiting machines to 113 dB(A) forced MV to redesign the cylinder head and fit mufflers, reducing performance. Barry Sheene's Suzuki dominated the season, and Agostini failed to reach a podium for most of the year, switching to a Suzuki RG 500 after the second round.
The final race appearance of the MV Agusta 500 Four came on 29 August 1976 at the Nürburgring Nordschleife. Equipped with lighter pistons and a lighter crankshaft, Agostini won in difficult conditions by 52 seconds over Marco Lucchinelli — a result that stands as the last victory by a four-stroke machine in direct competition against two-stroke Grand Prix engines.
After the Nürburgring race, MV Agusta officially ended its motorsport programme. A new majority shareholder declined to fund the racing department of a financially troubled company. A water-cooled four-cylinder boxer prototype had been in development but never advanced beyond that stage. In 1978 Cagiva attempted to purchase the MV Agusta racers to serve as a basis for their own programme, without success.