Matra's sports prototype program expanded rapidly in the late 1960s as the French manufacturer sought to challenge established Italian and German competitors in endurance racing. The MS650 represented an evolution of the earlier MS630, retaining the fundamental layout while incorporating improvements suited to the Group 6 regulations governing the International Championship for Makes. Development was conducted in partnership with Simca, whose name appeared on the car alongside Matra's.
The MS650 made its competition debut at the 1969 24 Hours of Le Mans, where Matra entered a four-car assault mixing the new model with older MS630 variants. Jean-Pierre Beltoise and Piers Courage drove the MS650 to a fourth-place finish, a strong result in the car's inaugural outing. Jean Guichet and Nino Vaccarella took fifth in an MS630, with Nanni Galli and Robin Widdows following in seventh. Johnny Servoz-Gavin and Herbert Müller were less fortunate, retiring their MS630/650 due to an electrical failure.
Later in the season, Matra entered two cars for the 6 Hours of Watkins Glen. Servoz-Gavin and Pedro Rodriguez brought their MS650 home in fourth place, while Guichet and Widdows retired from the sister car with a broken clutch. At the final round of the season, the 1000 km of Zeltweg, only Servoz-Gavin and Rodriguez were entered, but they retired following an accident. Matra finished the 1969 International Championship for Makes in fifth place with six points.
The 1970 season saw Matra field the MS650 more extensively before transitioning to the new MS660. At the 24 Hours of Daytona, the team entered cars for Jack Brabham and François Cevert, who finished tenth, and Jean-Pierre Beltoise alongside Henri Pescarolo, who came home eighteenth.
At the 12 Hours of Sebring, revised pairings saw Pescarolo and Servoz-Gavin finish fifth and Cevert paired with Dan Gurney coming twelfth. The 1000 km of Brands Hatch brought Brabham and Beltoise together for a twelfth-place result, while Pescarolo and Servoz-Gavin retired with engine failure. Both cars finished the MNZ race, with Brabham and Beltoise fifth and Pescarolo and Servoz-Gavin sixth. Matra skipped the Targa Florio, the 1000 km of Spa-Francorchamps, and the 1000 km of Nürburgring.
At the 1970 24 Hours of Le Mans, the team entered three cars: Beltoise and Pescarolo drove the new MS660, while Brabham and Cevert, plus Patrick Depailler, Jean-Pierre Jabouille, and Tim Schenken, campaigned MS650s. All three cars retired with engine failure, ending an otherwise promising campaign at the circuit where the MS650 had scored its best result a year earlier. Matra did not contest the final two rounds of the 1970 season, finishing fourth in the championship with four points.
The MS650 fulfilled its role as a transitional machine in Matra's endurance racing story, bridging the gap between the early MS630 era and the dominant MS660 and MS670 programs that would follow. Its competitive debut at Le Mans in 1969, where it recorded a fourth-place finish on first appearance, demonstrated the promise of Matra's engineering. The car provided valuable experience for drivers including Beltoise, Pescarolo, Cevert, Servoz-Gavin, and Rodriguez, many of whom went on to contest the later and more successful chapters of Matra's sports car campaign.