After the German Ministry of Aviation (RLM) found out about the new American B-29 Superfortress in 1942, serious concerns were raised among high ranking officials, questioning the Luftwaffe’s ability to deal with such a new potential threat. At the time, the B-29 flew higher and faster than any fighter the Luftwaffe had at their disposal and the only weapon that could effectively counter it was the 12.8cm FlaK 40 heavy AA cannon. This led to the development of a range of new German high-altitude fighters, interceptors and dedicated bomber hunters.

The first prototype of the Ju 388 performed its maiden flight in December 1943, showing promising results. After the construction and testing of six further prototypes were completed in three modifications: the Ju 388J high-altitude interceptor, a Ju 388K medium bomber and the Ju 388L scout. The Ju 388 was ordered into production and was officially introduced into Luftwaffe service in summer 1944. However, initial production progressed at a slow pace due to the limited availability of the required engines for the aircraft. Furthermore, the continuously worsening war conditions in Germany had a severe impact on overall production, eventually preventing it entirely by the end of the war.

In the end, only around 100 Ju 388s were built with most aircraft seeing only limited action during their short service life during the final stages of WW2.