From 1906 to 1914, it was served by long-distance services, which ended after the First World War and the subsequent reincorporation of Alsace-Lorraine into France.

Originally the administration of the Circle of the Rhine (Rheinkreis), which was part of Bavaria, planned that its first railway line would be first in the north–south direction.

Instead, the Palatine Ludwig Railway (Pfälzische Ludwigsbahn) was built between 1847 and 1849 from Rheinschanze (Ludwigshafen from 1853) to Bexbach; this mainly served the transport of coal.

There were two options for discussion: one would run from Neustadt via Landau to Wissembourg in Alsace and continue from there to Strasbourg.

[4] The section to Germersheim was opened on 14 March 1864 at a cost of a total of one million gulden, after being delayed by difficulties on agreeing on a route past its fortress.

[6] The municipality of Kandel, which since 1864 had been served by the line from Winden to Karlsruhe campaigned for a route that passed through its territory.

The construction of the line went forward without any major problems and it was opened on 25 July 1876, along with its continuation via Lauterbourg to Strasbourg.

[7] The express trains from Berlin to Strasbourg, which had previously run via Neustadt and the Neustadt–Wissembourg railway, now ran via Speyer and Germersheim as this route was shorter and the new track provided sufficient capacity.

After the First World War, Alsace-Lorraine was returned to France and the long-distance services to it also ended, since the newly founded Deutsche Reichsbahn wanted trains to run as far as possible within Germany.

The Reichsbahn allocated the line to the newly created Reichsbahndirektion (railway division) of Ludwigshafen in 1922.

In 1936 the route line was reallocated during the dissolution of the latter – with the exception of Wörth station – to the railway division of Mainz.

[10] In the course of the staged dissolution of the railway division of Mainz from 1 August 1971, its counterpart in Karlsruhe took responsibility for the station.

Between Germersheim and Wörth, the platforms of the stations that already existed before 2010 differ from the other Stadtbahn platforms in the area of the Karlsruher Verkehrsverbund (Karlsruhe transport association, KVV) in having a length of 160 m to allow the commuter trains to and from BASF to stop there.

The usual platform length for a triple set is 120 m. Both tracks, including all points, were completely replaced over the whole Germersheim–Wörth section during the summer holidays of 2007.

Because of finds of unexploded bombs from the Second World War in the track bed in the area of Jockgrim the construction work was extended by a week.

While still in the city of Speyer it curves again to the southwest and runs almost straight, passing the community of Römerberg to the west of its built-up area.

The halt of Speyer Nord-West (northwest) connects the suburbs of Speyer-Nord and Speyer-West to the rail network.

[12] The development programs for Rheinland-Pfalz-Taktes 2015 (the Rhineland-Palatinate integrated regular interval timetable for 2015) and for the second stage of construction of the Rhine-Neckar S-Bahn included the construction an additional halt in the south of the city of Speyer, called Speyer Süd.

After ten years of delay, the city council of Speyer decided in August 2012 to build the halt at Dr.-von-Hörmann-Straße in the immediate vicinity of the Speyer-Südwest special area.

It is at the extreme northern end of the city and its track layout is partly in the municipality of Lingenfeld.

It was opened at the end of 2010 during the integration of the Germersheim–Wörth line in the network of the Karlsruhe Stadtbahn and is – since the Bruhrain Railway is slightly elevated on an embankment – like Ludwigshafen Hauptbahnhof in having diverging platforms on different levels.

[16] Previously, it connecting line to a US oil terminal and one to the Büromöbelfabrik Kardex furniture factory.

It was opened at the regular 2011/2012 timetable change on 10 December 2011 and thus only one year after the commencement of Stadtbahn operations between Wörth und Germersheim.

Light-rail sets of classes GT8-100C/2S and GT8-100D/2S-M operate at least hourly between Germersheim and Wörth as Stadtbahn lines S51 (Germersheim–Wörth (Rhein)–Karlsruhe Albtalbf–Karlsruhe Europaplatz/Post Galerie (Karlstr.))

They were previously operated with electric multiple units of class 425, as are services on the Rhine-Neckar S-Bahn.

Since March 2015, this service, which is now part of the new Süwex network, has been operated with class 429 (Stadler FLIRT) sets.

The ports of Speyer, Germersheim and Wörth are served; furthermore, block trains are operated, mainly to the Mineralölraffinerie Oberrhein oil refinery in Karlsruhe and to BASF in Ludwigshafen.

The rolling stock formerly used in rail freight operations was based in the Ludwigshafen locomotive depot in particular.