Müllheim station is located on the southernmost portion of Rhine Valley Railway, about halfway between Freiburg and Basel.

Müllheim station was opened on 1 June 1847, along with the Freiburg–Müllheim section of the Rhine Valley Railway, which connects Mannheim via Karlsruhe and Freiburg to Basel.

The train driver had fallen asleep and the subsequent enquiry considered the effects of alcohol on driving for the first time in Germany.

The Baden government published an act on 30 March 1872 for "the creation of a railway from Müllheim to Neuenburg and possibly continuing to Mulhouse.

Since 9 December 2012, there are up to seven services daily between Baden and Alsace, with at least one pair of trains running directly to and from Freiburg Hauptbahnhof.

[10] The station building was demolished in July 2022, so that high speed tracks could be built in its place for the Karlsruhe–Basel high-speed railway.

Since December 2013, Müllheim has been served by a daily InterCity service (the Baden-Kurier) on the route between Basel Bad and Munich.

Since August 2013 a pair of TGV services have run between Freiburg and Paris via Mulhouse, which made a technical stop in Müllheim until December 2015, but passengers were not able to embark or disembark.

Intercity-Express trains stopped at Müllheim station every hour from April to October 2014 due to construction work on the old railway line between Schliengen and Efringen-Kirchen.

These are usually performed with French X 73900 sets owned by TER Alsace and operated by Deutsche Bahn as Regionalbahn services.

[17] After the completion of the third and fourth tracks as part of the Karlsruhe–Basel high speed line, an hourly service from Mulhouse via Müllheim and Freiburg to Sasbach is envisaged under the Breisgau S-Bahn 2020 proposal.