It ran from Heidelberg via Neckargemünd and Meckesheim through the Little Odenwald mountains to Waibstadt, Mosbach, Osterburken and Lauda to Würzburg in Bavaria.

The plans in the mid-19th century to build a railway network in the Grand Duchy of Baden, initially focused on the construction of the Baden Mainline as a north–south route through the Upper Rhine Valley from Mannheim to Basel as well as a connection through the Lake Constance area to Constance.

Therefore, from the 1850s, ever louder demands were raised for a connection to the rail network from the poor areas in southern Odenwald, in the Bauland and in the Tauber valley (mockingly known as Badisch Sibirien, Baden Siberia, because of its small population, cold winters and isolation from the rest of Baden).

[2] The Baden Odenwald Railway was opened in two stages: from Heidelberg via Neckargemünd, Meckenheim Neckarbischofsheim, Aglasterhausen and Neckarelz to Mosbach on 23 October 1862 and from Mosbach to Würzburg via Osterburken and Lauda on 25 August 1866.

As a result, the individual sections of the Odenwald Railway developed very differently: This section is now considered to be part of the Neckar Valley Railway (Heidelberg–Heilbronn) opened in 1879 and serves passengers and freight between the Palatinate and the Stuttgart area.

Along with the Neckar Valley Railway, it creates a second connection between Heidelberg and Heilbronn.

Of all the sections of the Odenwald Railway this had the least volume of traffic and was downgraded to a minor line.

This would have meant that Krebsbach Valley Railway (Krebsbachtalbahn), which had existed since 1902 and branches off at Neckarbischofsheim Nord and runs to Hüffenhardt, would have had no connection to the rest of the rail network.

Thus, in the 1970s between Osterburken and Lauda stops at all stations were temporarily abandoned due to the sparse population.

From the turn of the millennium, services were reactivated at some of them, such as Rosenberg (Baden), Eubigheim and Boxberg / Wölchingen, which are significant for school transport, and they are served on weekdays by a few Regionalbahn trains.