From 1891 to 1939, the metre gauge Frankenthal–Großkarlbach Local Railway (Lokalbahn Ludwigshafen–Großkarlbach) ran from the station to Großkarlbach.

During the construction work there was a dispute between the Deutsche Bahn and the municipality of Frankenthal in relation the width of the platform on track 2.

Deutsche Bahn reduced the width of the platform due to underground cables, which was criticised by the municipality.

The new S 6 line of the Rhine-Neckar S-Bahn, which stops in Frankenthal, went into operation at the summer timetable change on 10 June 2018.

The three platform tracks of Frankenthal station are over 300 m long and still have a height of 76 cm and provide barrier-free access to the trains.