Presbyterian Ladies' College was founded in 1875 and is one of the first public school for girls in Australia still in existence. The College was situated in East Melbourne , and its initial enrolment was 60 students. Among its students in that first year were Catherine Deakin, sister of future Prime Minister, Alfred Deakin, and Ellen Mitchell who was to become Dame Nellie Melba.

When the University of Melbourne opened its doors to female students in 1881, many were from the College: Constance Ellis, the first Victorian woman to receive the degree of Doctor of Medicine, Flo Greig, the first woman to be admitted to the Victorian Bar; Ethel Godfrey, Victoria's first woman dentist; and Vida Goldstein, suffragette and the first woman to stand for election to Federal Parliament.

In 1939, with 600 pupils and 40 teachers, accommodation at East Melbourne was strained and 'Hethersett', a residence in extensive grounds in Burwood in the developing residential suburbs 15 kilometres to the east, was purchased.

The Junior School moved to the new site that year and in 1958 was joined by the Senior School and Boarding House, all in new purpose-built buildings.

In 1980, the College was incorporated, retaining its links as an educational institution in connection with the Presbyterian Church of Victoria.

The College maintains its tradition of educational leadership. Many of today's prominent Australian women were educated at Presbyterian Ladies' College. Two former students of the College have been awarded Rhodes Scholarship in the past ten years.

Today, PLC’s international outlook, recognised by the Council of International Schools, reflects a student population that blends diverse cultural backgrounds, languages, religious practices and political systems.

Within the twin contexts of life in democratic Australia and teaching and learning at PLC, a Christian independent girls’ school, there is a commitment that our programs and teaching support and promote the principles and practice of elected government, the rule of law, equal rights for all before the law, freedom of religion, freedom of speech and association and the values of openness and tolerance.