A treaty between the Grand Duchy of Baden and the Kingdom of Bavaria authorised the building of a railway line from Bruchsal to Germersheim.

In August 1874, after an agreement was reached regarding the location of the bridge over the Rhine, the plan to extend the line to Germersheim was approved and work began on 9 April 1875.

The Bruhrain Railway was from 1890 used for the first time as part of an inter-regional connection, running on the Bruchsal–Germersheim–Landau–Biebermühle–Zweibrücken–Saarbrücken route.

In addition, long-distance trains also ran from that time between Munich and Saarbrücken on the Bruhrain Railway.

Opponents of the reconstruction highlighted the small importance of the bridge for traffic, yet approval for the work was announced in 1964.

From the spring of 2000, the Regional-Express line was introduced on the Mainz–Germersheim–Karlsruhe route every two hours, which travelled over the Germersheim–Graben-Neudorf section of the Bruhrain Railway.

The platforms were then raised to a height of 76 cm and extended to a length of 140 m (corresponding, for example, to two class 425 multiple units).

As of May 1994, the Bruhrain Railway also benefited from two improvements to its services: firstly, through the establishment of the Karlsruher Verkehrsverbund (Karlsruhe Transport Association, KVV), which has since managed services on the railway as line R 9; and, secondly, the introduction of the Rhineland-Palatinate integrated regular interval timetable (Rheinland-Pfalz-Takt).

Hourly services were introduced under the new timetable, including for the first time since 1945 through trains on Sundays.

On the Graben-Neudorf–Germersheim section Regional-Express (RE) services run every two hours on the Karlsruhe–Speyer–Germersheim–Mannheim–Worms–Mainz route, using class 429 multiple units.

Between Philipsburg and Rheinsheim, however, there is a siding to the Philippsburg Nuclear Power Plant, which is served by a few freight trains.

From the early 1990s until the introduction of the Rhine-Neckar S-Bahn there were services on the Bruchsal–Germersheim–Ludwigshafen–Mannheim–Heidelberg–Neckargemünd–Meckenheim–Sinsheim–Steinsfurt–Eppingen/Heilbronn route, operated with locomotives of class 218 hauling Silberling carriages.

Since the integration of the Bruhrain Railway in the Rhine-Neckar S-Bahn in December 2011, some services continue past Germersheim.