The first Kleist Museum was opened in 1922 on the ground floor of Heinrich von Kleist's birthplace at the suggestion of the Kleist Society; in 1937 it was given a new home in the Oderland Museum as the Museum for Heinrich and Ewald Christian von Kleist. Both the birthplace and the building of the Oderland Museum were destroyed in April 1945. In July 1953, on the occasion of the 700th anniversary of the city of Frankfurt an der Oder, a new Kleist memorial was opened, which - looked after by the city archive - presented the rescued objects in two rooms of the city library. As an independent institution, the Kleist Memorial and Research Centre moved into the current old building, the former Garrison School, in 1969.

Since October 2013, a modern new building has flanked the baroque building. By structurally connecting the old and new buildings, the old building was made accessible to the disabled, and it was also possible to create conservationally appropriate conditions for housing the collections and user-friendly workplaces. This has doubled the exhibition space.