The Sandersleben–Blankenheim section has only a single track, while the remainder of the still-operating parts of the line is duplicated.

The track was built at the instigation of the Prussian government between 1877 and 1882 as a direct militarily strategic railway, bypassing urban areas, connecting to Alsace-Lorraine, which had been acquired from France as a result of the War of 1870-71.

For long-distance traffic between Berlin and western and south-western Germany, other routes via Magdeburg, and Halle or Leipzig were more important.

In 1961, the section from Drewitz (now Potsdam Medienstadt Babelsberg) to Berlin–Wannsee was closed to passenger traffic, as a result of the building of the Berlin Wall.

Catenary stanchions for electrification were established in the Güterglück and Blankenheim areas, but no further work was carried out.

It was used by Intercity-Express and Intercity trains during construction work on the Berlin-Potsdam-Magdeburg line completed on 14 December 1995.

In the Berlin suburbs, all S-Bahn, regional and mainline services to Potsdam run on the Berlin-Blankenheim line.