All rail tracks are in Mannheim, only the station building is located on the territory of the Edingen-Neckarhausen hamlet of Neu-Enghien.
The Bensheim–Heidelberg section was opened together with the branch from Mannheim and thus the whole length of the Main-Neckar Railway was completed on 1 August 1846 in Friedrichsfeld.
On 1 June 1880 the line from Mannheim-Friedrichsfeld to Schwetzingen was put into operation, which is almost exclusively used by freight traffic.
Mannheim-Friedrichsfeld station belongs to the fare zone of the Verkehrsverbund Rhein-Neckar (Rhine-Neckar Transport Association, VRN).
The station is also the starting point of Regionalbahn services via Mannheim to Mainz, which in the weekday peak hour occasionally begin or end in Bensheim.