This railroad line was built in 1883 by the St. Louis and Cairo Railroad, which later became the Mobile & Ohio Railroad. According to local history, on April 2, 1912, a derailment occurred on the line west of Millstadt in which the engineer, William Strauss, and the brakeman, Arthur Swinderman, were killed.
The tracks were abandoned in 1961 as railroad service to Millstadt ended.