Summarized from von Gersdorff et al.:
Based on 1936 Jumo studies for a 1800 PS engine, in 1937 the RLM ordered a 1900 PS engine (24 cylinders, liquid-cooled) for left- and right-handed operation. Ferdinand Brandner, who was new at Junkers, was to develop this engine, which he projected as a 2000 PS, 6 rows of 4 cylinders design. It ran first in 1939 and in 1940 developed 2000 PS on the dynamometer and was flown as middle engine in a Ju 52. In 1941, it completed a 100 hour test on the dynamometer. In the meanwhile, combat experience had caused the RLM to demand more from the Ju 288 (which was to be the main user of the Jumo 222) than originally planned, and it turned out it would need 2 x 2500 PS instead of the 2 x 2000 PS of the Jumo 222 provided. Preparations for series production (which had progressed very far) were stopped.
There were two main causes for the teething problems of the Jumo 222: Inferior main and connection rod bearings (for lack of tin, a strategic material) and inferior lubrication properties of the synthetic lubricants.
The next generation of Jumo 222 engines had an increased bore for increased power. In December 1942 a 100 hour test at 2500 PS was completed successfully. However, in the summer of 1943 the Bomber B was cancelled due to the change of the strategic situation, and Jumo's priorities shifted to the Jumo 213 which was better suited for the use in fighters.
In April 1944, Dessau was bombed heavily, necessitating the move of Jumo 222 production and development to Oberursel. The power requirement increased again to 3000 PS, leading to another increase of bore and stroke. This generation was split into an advanced high-altitude engine with two-stage, hydraulically driven supercharger with charge mass control and intercooling and MW50 and GM-1 boost for 2500 PS (dry), and a less sophisticated mid-altitude engine of 3000 PS.