It comprised the mostly rural eastern part of Brandenburg, including the New March and Lower Lusatia.

In 1938 the districts of Arnswalde and Friedeberg [de] were disentangled from the Frankfurt Region and merged into the new government region called Frontier of Posen-West Prussia, which was incorporated into the Province of Pomerania.

At the same time the districts of Meseritz and Schwerin (Warthe), were transferred out of what had previously been defined as the Province of Posen-West Prussia, now becoming part of the Frankfurt Region.

West of the Oder–Neisse line, the Land of Brandenburg, created in 1946, was not administratively subdivided into "government regions".

Three years later, however, the newly evolving East German state undertook further administrative reforms in 1952 and the western areas of the former Frankfurt Region became part of the new Frankfurt Bezirk (district).