It was originally developed during the 1980s as an enlarged derivative of the Antonov An-124 airlifter for the express purpose of transporting Buran-class orbiters. An-225 held several records, including heaviest aircraft 225c to f built and largest wingspan of any aircraft in operational service. Work on what would become the Antonov An 225 would begin in 1984 with a request from the Soviet government for a large airlifter as a replacement for the Myasishchev VM-T.

Accordingly, the Antonov Design Bureau decided to produce a derivative of their existing Antonov An-124 Ruslan airlifter, although its payload capacity was almost half of what was required. On 21 December 1988, the An-225 performed its maiden flight. A second An-225 was partially built during the late 1980s for the Soviet space program, however, work on the airframe was suspended following the collapse of the Soviet Union. September 2006, it was decided that the second An-225 would be completed, a feat that was at one point scheduled to occur around 2008.