Plans were developed and the president of the Prussian administration in Cologne, Daniel Heinrich Delius, gave his conditional support for them.

The Dutch government subsequently instructed its chief engineer for public works, Bernard Herman Goudriaan to develop a route for the line.

[2] As a result, it was proposed the new railway would run from Amsterdam via Amersfoort, Isselburg, Hamminkeln, Wesel and Duisburg to Cologne, avoiding large cities such as Utrecht and Arnhem in order to minimise the risk of floods disrupting the line.

[2] During the following years several proposals were submitted and rejected until on 18 July 1851 the two governments signed the "Prussian-Dutch agreement for the construction of the Oberhausen–Wesel–Emmerich–Arnhem railway".

On 30 December 1852, the Cologne-Minden Railway Company (Cöln-Mindener Eisenbahn-Gesellschaft, CME) was granted a concession to build the line on condition that construction was completed within three years.

[2] The final route of the line was eventually approved by the Prussian Minister of Trade, Commerce and Public Works on 4 May 1854.

[2] Following a construction period of two years, the Oberhausen-Dinslaken section was opened on 1 July 1856 and the entire double-track line was put into operation on 20 October 1856.

The destroyed Wesel Railway Bridge over the Rhine was not rebuilt, ending operations on the lines to Boxtel and Venlo.

The EuroCity trains were mostly replaced in November 2000 by Intercity-Express (ICE) services between Amsterdam and Cologne, using modern multi-system electrical multiple units capable of high-speeds, which no longer needed to stop in Emmerich.

In July 2013, the German federal government, the state of North Rhine-Westphalia, Deutsche Bahn and other parties signed a €1.5bn funding agreement to upgrade the 73 km Emmerich-Oberhausen segment.

[3] The Oberhausen–Arnhem railway is served every two hours each day by long-distance passenger services operated by ICE International trains on the Amsterdam Centraal–Utrecht Centraal–Köln Hbf–Frankfurt (Main) Hbf / Basel SBB route.