The work of St Anthony’s was started in the late 19th and early 20th centuries by the St Vincent de Paul Society in the inner city of Sydney. Two of their main initiatives were the care of abandoned children and young unmarried mothers. In the 1920s the St Vincent de Paul Society purchased a house at Petersham as a residence for pregnant girls and orphaned children. They soon outgrew these premises and the service was moved to the present location at Alexandra Avenue, Croydon.
Throughout the first half of the 20th century the demand for accommodation for unmarried mothers continued to grow and new buildings were erected on the site. At one stage there was a Mothercraft teaching facility for nurses as well as a maternity hospital on the Croydon site.