[3] The College is owned by the Congregation of Dominican Sisters of Eastern Australia and the Solomon Islands[4] and located within the Archdiocese of Sydney.

Eight Dominican sisters arrived from Ireland in 1867, to establish schools for Catholic children in New South Wales.

[9] Although the College saw its first student matriculate in 1906, it was not officially recognised as a secondary school until 1912, with the passing of the New South Wales Bursary Act.

[9] In 1936, Santa's most prominent building, Holyrood—originally built as Illyria by industrialist Charles Hoskins in the early 1890s—was purchased from William Adams of the Tattersall's Hotel.

[9] The Del Monte property, located across the road from the College, was leased in 1949, with the first primary school students taking up residence later that year.

Santa Maria del Monte was expanded in 1968, with the purchase of Lauriston,[9] which had been the home of the Presbyterian Ladies' College, Sydney during the Second World War.

[11] 1996 saw the establishment of the Out of School Hours Centre (OOSH), and in 1997, a property at Tallong was purchased for outdoor education.

In 1998, Mary Bailey House was opened as an Early Childhood Centre, and in 2002 classes for Years 6 and 7 commenced at the middle school campus, Martin De Porres.

The Strathfield campus includes a 33-metre (108 ft) outdoor swimming pool, six tennis courts, three ovals and a chapel.