The South Harz line runs roughly east–west, with Northeim lying further north than Nordhausen.

Near Tettenborn, at Sachsenstein near Walkenried and near Woffleben there are problems with subsidence: the load-carrying capacity of the soil must be regularly controlled.

During the building of the Walkenried Tunnel in 1868, the miners discovered the unstable Himmelreich cave, which made construction difficult.

The South Harz line was opened on 1 December 1868 from Northeim to Herzberg and it was put into operation to Nordhausen on 1 August 1869.

Since the completion of the Solling Railway from Ottbergen to Northeim in 1878, it was part of the shortest route between Cologne and Leipzig.

From 1899 to 1963, Walkenried was a terminus of the metre gauge line of the South Harz Railway Company (Südharz-Eisenbahn-Gesellschaft) to Braunlage.

Later Scharzfeld station was also closed and it was replaced from the timetable change on 11 December 2005 with a new halt called Bad Lauterberg im Harz–Barbis.

Signalling on the South Harz line will in future use electronic interlockings that are remotely controlled from a centre in Göttingen.

The camp was attached to the vast underground Mittelwerk weapons factories for building V-2s and V-1 flying bombs.

The South Harz line is served by Regionalbahn services operated by DB Regio Niedersachsen.