The Grand Trunk Railway came to St. Marys in 1857, sixteen years after the founding of the settlement. The first station, a limestone structure (c. 1858), was inconveniently located a few kilometers northeast of the Town centre just east of the railway junction with the main line heading to Sarnia and the branch line heading to London. This first station, now being the best preserved of all the original GTR stations in Ontario, is a National Historic Site and the property is designated under the Ontario Heritage Act. The second station, a wooden building built in 1879 and now demolished, was more conveniently located at the “Switch” on the branch London line (two blocks south of this St. Marys VIA Station). Train service brought prosperity to the village with increased trade, access to distant markets for farm produce and limestone, and a contribution to population, commercial and industrial growth.

In 1907 the third station, being the current brick passenger station, was built, and it has always meant a great deal to the people of St. Marys. This property is designated under the Ontario Heritage Act and is referred to as the St. Marys VIA Station.