On 18 December 1843, the Prussian government granted a concession to the Cologne-Minden Railway Company (German, old spelling: Cöln-Mindener Eisenbahn-Gesellschaft, CME) for the line, which began at what was then the CME station in Deutz (now a suburb of Cologne) with the construction of the first section to Düsseldorf, which was opened on 20 December 1845.

The route of the next section to Oberhausen, Altenessen, Gelsenkirchen, Wanne, Herne and Dortmund to Hamm was chosen over a route close to the coal mines that were then located on the north bank of the Ruhr because it was cheaper to build as it largely avoided hills.

On 15 October 1847 the last section was opened to Minden, thus completing the entire 263 kilometre long, single track railway.

There are six tracks past the S-Bahn branch to Düsseldorf Airport Terminal station to Düsseldorf-Unterrath Karthäuser Weg junction where the S-Bahn and two long distance-tracks merge at grade on the approach to Düsseldorf Airport station.

This makes it possible to operate trains between Cologne and Dortmund via Duisburg in the same time as it takes on the shorter but more tortuous route via Wuppertal and Hagen.

Between Düsseldorf and Duisburg additional services operating are the RE 2 Rhein-Haard-Express, the RE 3 Rhein-Emscher-Express, the RE 6 Rhein-Weser-Express, the RE 11 Rhein-Hellweg-Express and the RE 19 Rhein-IJssel-Express (all hourly).