In the 1840s the Württemberg government decided to build a rail link to the Rhine Valley Railway to connect to Mannheim and the nearby industry.

After years of negotiations between the Kingdom of Württemberg and the Grand Duchy of Baden, an agreement was reached on the route of the Western Railway on 4 December 1850.

The line branched from the Northern Railway in Bietigheim, running for 23 km until it reached a point between Weilern Eckenweiher Hof and Mühlacker.

Experts of both countries criticized the route of the line because it prevented the important town of Vaihingen having a well-located station.

Baden criticized the location of an important frontier station at a secluded farmhouse.

Unusually for Germany, the new station was named after the locality of Mühlacker, not after the community that it was part of.

From the southwest the Grand Duchy of Baden State Railway (Großherzoglich Badische Staatseisenbahnen, BadStB) opened its line from Durlach on 1 June 1863.

On 5 June 1883 the Orient Express ran for the first time on the line from Paris Gare de l'Est to Giurgiu (now in Romania).

The new line would run via Sternenfels, Diefenbach, Freudenstein, Maulbronn, Schmie and Lienzingen to Mühlacker.

In 1941 a new connecting curve was built at the west of the station between the Karlsruhe–Mühlacker line and the Western Railway towards Bruchsal.

This allowed trains running from Pforzheim towards Bruchsal to avoid reversing in Mühlacker station and therefore had a strategic advantage for moving troop transports faster towards France.

The commissioning of the new line on 2 June 1991 meant that only a few express trains continued to run through Mühlacker.

The former border station resumed its old role as a nodal point with dense regular interval operations and long-distance connections.

A striking feature of the Western Railway stations was their entrances, which were highlighted with alternating red and yellow sandstone.