The first bishop of the Diocese, James Francis Corbett, was a priest of the Diocese of Limerick, Ireland, who was responsible for the Mission (later Parish) of St Kilda and Chancellor of the Archdiocese of Melbourne at the time of his appointment.

Bishop Corbett consecrated St Patrick's Cathedral, Melbourne, on account of his superior vocal ability.

The second Bishop of Sale, Patrick Phelan, saw to the establishment of a school system in the Diocese.

The fourth bishop, Patrick Lyons, saw the 1959 change to the boundaries of the Diocese, which incorporated into Sale from the Melbourne Archdiocese the parishes of Berwick, Cranbourne, Pakenham, Iona, Maryknoll, Koo Wee Rup, Dalyston and Korrumburra.

Purpose-built as a cathedral, St Mary's boasts a Romanesque onyx high altar, notable stained glass windows and a large statue of Mary Help of Christians as its features.