On 31 July 1943 the unit was declared operational, with a total of 19 aircraft. On 17 August 1943 the unit was one of those who intercepted American bomber forces attacking the Messerschmitt factory in Regensburg and the ball bearing plants in Schweinfurt. Grislawski claimed two Boeing B-17 Flying Fortresses downed on this raid. On 6 September the unit's pilots shot down four Flying Fortresses over Stuttgart, one to Grislawski, and two claimed by Graf with the WfGr.21, who was then shot down but survived a forced landing. Grislawski claimed one other kill with the unit, a B-17 on 14 October.
In around four months of operations Graf was the sole pilot of JG 50 to down a Mosquito, which he caught after loitering at 30,000 feet over Groningen.
By October, JG 50 had been disbanded and merged with I Gruppe, JG 301.