The township of St Marys was originally known as South Creek and changed to St Marys in 1885.  It was named after the church of St Marys Magdalene and was consecrated in 1840, the year the Post Office opened.  The church is heritage-listed and is one of the oldest in New South Wales that still has regular services.

The Bennett coach and wagon works commenced in 1858 manufacturing horse-drawn wagons to meet the growing demand for transport in Sydney and eventually closed in 1958.  At the end of the 19th century they were employing around 25 men with their wagons selling between 150 – 250 pounds. 

In 1861 the population of St Marys was 444 and by 1891 had risen to 1,823.  The village also expanded its industries with tanneries, sawmills, brick makers and wheelwrights developing from the use of local natural resources.  The railway station opened in 1862 but the focus of the town remained along the Great Western Road.  Work from Parramatta to St Marys (previously known as South Creek) began in 1858. 

Queen Street runs north from the Great Western Highway to the railway station and was once known as Dickson Lane, Mamre Road, Windsor Road, and later Station Street, before being renamed Queen Street in June 1897 after Queen Victoria to celebrate her Diamond Jubilee.  Queen Street is now the main street of St Marys Town Centre and is characterised by traditional shop fronts and wide pedestrian walkways.