The line was built by the Magdeburg–Leipzig Railway Company (German: Magdeburg–Leipziger Eisenbahn-Gesellschaft), with construction starting on 24 January 1838.

It was the first German railway that passed through several countries, in addition to the kingdoms of Prussia (Magdeburg, Halle) and Saxony (Leipzig), it also crossed the Duchy of Anhalt-Köthen.

On 29 April 1874, the Magdeburg–Leipzig Railway Company purchased the Saxon section of the line with effect from 1 January 1875.

On 1 May 1912 the Prussian part of the Leipzig Hauptbahnhof was opened, leading to the closure of the Magdeburger station.

Currently, the section between Magdeburg and Halle is served by Regionalbahn trains that run hourly and are made up of three double-deck carriages with control cars and propelled by class 143 electric locomotives.

Lines S3 and S5X of the S-Bahn Mitteldeutschland run between Halle and Gröbers or Wahren with Bombardier Talent 2 multiple units.