The city, located at the intersection of two historical roads, was first settled in 1810. It was named the seat of the new Elgin County in 1844 and was incorporated in 1852. It officially became a city in 1881.
In the late 19th century and early 20th century several railways were constructed through the city, and St. Thomas became an important railway junction. In the 1950s and 1960s, with the decline of the railway as a mode of transportation, other industry began to locate in the city, principally primary and secondary automotive manufacturing.