After years of planning and determination, St Euphemia College was established by the Greek Orthodox Community of Bankstown to uphold the Greek Orthodox culture and ethos within the local community. The official opening of the College took place on February 26, 1989, officiated by His Eminence Archbishop Stylianos.

The College commenced its first day of operation on 30 January 1989, with an enrolment of 29 students, spanning Kindergarten to Year 3. Mr Miltiades Yiangou served as inaugural Principal of the Primary School from 1989 to 2008. In 1993, the Secondary School began with an initial enrolment of 31 students, led by Mr Harry Hirakis. The school participated in the Higher School Certificate (HSC) for the first time in 1998. From 1998 to 2000, St Euphemia College was actively involved in the promotion of the Sydney 2000 Olympics. The school took part in the official opening of the State Hockey Centre in August 1998, as well as many other events. The highlight was the performance of the school choir, singing the Greek National Anthem at the closing ceremony of the Olympic Games.

In 2012, the College marked a significant moment with the expansion of its school facilities and grounds. The addition to the campus integrated the Primary and Secondary playgrounds, introducing a new College Hall, named the Peter Theophilou Wing and a library for the Primary School named the Father Michael Apostolopoulos Wing. The inauguration ceremony was attended by His Eminence the Archbishop Stylianos, Daryl Melham, Federal Member for Banks who represented the Australian Government and the Minister for School Education Peter Garrett. Peter Theophilou, OAM, the President of the local Parish-Community and the Board of Governors, expressed gratitude to the Federal, State and Local governments for their
contributions to the project. He acknowledged the historical importance of these new facilities, acquired through the Federal Government’s “Building the Education Revolution’ program.

In 2013, a grant from the Federal Government's Secure Schools Program, provided essential funds for St Euphemia College, enabling the implementation of security systems on the campus. The Prep class was introduced in 2018, aiming to facilitate a seamless transition for students into Kindergarten with a more gradual and comfortable entry into their formal educational journey.

The Very Reverend Father Peter Mavrommatis served as Principal of the College from 2019 – 2023.