It is part of an east-west line, known as the Mid-Germany Connection (German: Mitte-Deutschland-Verbindung), and is served by InterCity trains between the Ruhr and Kassel, Erfurt and Berlin.

However, Prussia had awarded the concession to build the line in its territory to the private Cologne-Minden-Thuringian Connection Railway Company (Köln-Minden-Thüringischen-Verbindungs-Eisenbahn-Gesellschaft, KMTVEG).

The cost of constructing the line, especially its 600-metre-long tunnel through the Eggegebirge overwhelmed the company and it filed for bankruptcy in 1848.

Freight traffic prior to 1945, however, mostly left the line at Altenbeken to run to Halle and Leipzig via Northeim and Nordhausen.

After the Second World War, north–south traffic increased to such an extent that the Hanoverian Southern line (Hanover–Göttingen–Kassel) was overloaded.

To relieve this traffic, a connection curve was established in 1958 in Altenbeken to enable Hanover–Kassel trains to run without reversing.

In December 1970, electrification of the line from Hamm via Warburg to Kassel was completed and travel time of luxury express trains (D-Züge) was shortened from 156 to 140 minutes.

Because of a landslide between Willebadessen and Neuenheerse in the spring of 1988, the section between Altenbeken and Warburg was blocked for weeks and long-distance trains were diverted on to the Göttingen–Bodenfelde line.

From 1973, the Deutsche Bundesbahn (German Federal Railways) tried to add branch lines to its successful InterCity network.

From 1990, Deutsche Bundesbahn, introduced the new InterRegio (IR) service in an attempt to attract new customers, with fast trains at regular intervals with short travel times and superior comfort.

In the 2009 timetable change individual IC train pairs were introduced, so there is no longer a regular interval service between Düsseldorf and Stralsund.

The Regional-Express service runs from Monday to Friday every two hours, taking the same time as IC trains.