​​​San Sisto in Rome was given to St Dominic in 1220 as a convent for the Dominican Sisters who still live there today. San Sisto College, Carina, Brisbane was founded in 1961, and the Dominican Sisters named the College after the historic convent in Rome. “San Sisto” means St Sixtus, in Italian. This was the name of one of the early Popes who suffered martyrdom for the Faith.

The first class of nine girls was housed in the present resource classroom in St Martin’s with Sister Josephine, Sister Callista and Sister Jude staffing the school. With the opening of the new Convent in November, 1961, the students took over the old Convent as the first San Sisto schoolhouse. In 1963 the first sod was turned for classrooms and in April, 1964, the official opening of classrooms was performed. The Aquinas and Music blocks and Staff room were opened in 1968 and in 1983, Home Economics, Science Rooms and the Library were added. In 1991, a new classroom block was added and in 1992 a new separate Library was built with the old library being converted to an additional Science Laboratory. As well, during 1992, tennis courts and a covered sports area were built. In 1978, the Catholic Education Office of the Brisbane Archdiocese assumed the responsibility for the administration of the College. A School Board (Pastoral) was established in 1992. In 2008, the sports area was changed into a state-of-the-art sports centre and auditorium and was named the Siena Centre, in honour of Catherine of Siena.

The College has continued to prosper and grow from its beginning of nine students in 1961. When the College commenced, the students were drawn largely from Our Lady of Graces Parish. Students now enrol from approximately forty-five feeder schools in the surrounding suburbs. However the influence of​ the Dominican Tradition of justice and learning is still felt in the lives of students, parents and staff members. Students are continually reminded of the historical background of San Sisto College through the four Sports Houses named Catherine, D​ominic, Jude and Rose.

A special day of celebration is held each year on the last day of Semester 1. Traditionally this day is commemorated with a College celebration of the Eucharist and activities organised by the College.​