In 1934, Daimler-Benz began designing the DB 600, the first of a highly-successful engine series. The DB 600 A/B was a supercharged, inverted V-12 rated at 746 kW (1,000 shp). Prototype deliveries began in December 1935. The DB 601, incorporating direct fuel injection and variable-speed supercharger drive, followed in 1936. Power ratings of the DB 601 ranged from 820 kW (1,100 shp) to 2,066 kW (2,770 shp) in the highly-modified Weltrekordmotor Re 5. Among aircraft powered by the DB 601 were the Messerschmitt Bf 109 and Bf 110 and Heinkel He 111.

Production of the larger displacement DB 603 began in May 1942, with the DB 603 A-2 introduced in 1944. A total of 8,758 DB 603 engines were produced in a number of different versions ranging in power from 1,245 to 1,685 kW (1,670 to 2,260 shp). Airframe applications for the DB 603 included the Focke Wulf Fw 190 and Ta 152B/C, and Messerschmitt Me 410.