The Heidelberg–Neckargemünd section of the line was built in 1862 as part of the Baden Odenwald Railway (Baden Odenwaldbahn), running from the Heidelberg via Neckargemünd, Meckenheim, Neckarbischofsheim, Aglasterhausen, Obrigheim, Neckarelz, Mosbach, Oberschefflenz, Seckach, Osterburken, Königshofen and Lauda to Würzburg.