Before Southern Cross Burwood opened, a previous school was established in 1909. The school closed down in 2010. In 2008, the Sydney Catholic Schools were successful in receiving The Australian Department of Education, Employment and Workplace Relations (DEEWR) funding. With this funding, the first round of Trade Training Centres (TTC) in schools came about, starting with a vocationally focused Senior Secondary College at Burwood.
With the appointment of its inaugural principal, Mr Patrick O’Reilly (2010–2019) Southern Cross Catholic College was founded in 2010 for this purpose. In 2021, the school changed its name to Southern Cross Catholic College to encompass the performing arts specialist stream.