The school was established by the Salesian Society in 1927, when Rupertswood Mansion, one of the largest private houses in Victoria, originally constructed for Sir William Clarke, was purchased from the estate of industrialist H. V. McKay.

Salesian College has a broad curriculum ranging from agriculture to visual communications, with its own sporting facilities, including a 25m swimming pool, a large stadium, a cross-country equestrian course, and a full-size football ground.

The school was exclusively served by the adjacent Rupertswood railway station, originally provided for Sir William Clarke, from 1962 until its closure in 2004.

"[8] Other priests from the college reached settlements with substantial compensation payments paid to their victims, over allegations of sexual abuse, but were not otherwise convicted.

[9][10][11][12] On 30 August 2013, David Rapson, a former vice principal, was found guilty of eight indecent assaults and five rapes committed against students at Salesian College between the mid-1970s and 1990.