The Magdeburg-Halberstadt Railway Company (German: Magdeburg-Halberstädter Eisenbahngesellschaft, MHE) opened the Magdeburg–Halberstadt line on 15 July 1843.

In 1967, the Langenweddingen rail disaster occurred on the line, the worst in the history of East Germany.

The accident involved a bi-level train hitting a tanker truck at a level crossing, resulting in an explosion that killed 94 people, many of them children on their way to a summer camp in the Harz mountains.

On 29 October 1988, the last scheduled steam-hauled train operated by East Germany railways ran between Thale and Halberstadt.

A collision between the Harz-Elbe Express and a freight train on the line on 29 January 2011 killed 10 people and injured 23.

[3][4] The halts of Hordorf, Krottorf and Groß Quenstedt have not been served since the timetable change on 9 December 2012.

It has duplicated sections from Hadmersleben to shortly before Oschersleben and between Krottorf and Groß Quenstedt.

The section between Halberstadt and Wegeleben is also duplicated, as part of the upgrading of the Halle–Halberstadt railway for tilting train operations.

The station building is located between the tracks and originally contained the customs and passport control facilities for travelling between the Duchy of Brunswick and the Kingdom of Prussia.

After the division of Germany after 1945, the route to Jerxheim was closed and in consequence the northern side of the station lost most of its purpose.

In recent years a few trains from Magdeburg terminated on the north side of the station.

Halberstadt station is a major transfer point to the northern Harz rail network.

Services on the line have been operated since 11 December 2005 for an initial twelve years by Transdev Sachsen-Anhalt as part of the Nordharznetz (north Harz network).

[8] The new bridge over the B 246 to the east of the Oschersleben (Bode) station has been usable since March 2017 and the road under it to be opened in November 2017.