However, construction was interrupted by the onset of the Great Depression, leaving a new transept and sanctuary, with the aisle of the original cathedral as its nave.

After being incomplete for 70 years, with portions of the cathedral requiring extensive repair work, funds were eventually raised in the late 1990s and early 2000s for the completion of the expansion.

The colony eventually outgrew this small church, and the local Bishop expressed an interest in constructing a "more worthy Cathedral".

[2] Bishop Serra therefore applied to the governor of the colony to cede the land in Victoria Square to the Roman Catholic Church, which occurred on 13 August 1859.

[2] He also secured a donation of marble from the Benedictine brothers of the Monastery of Saint Paul Outside the Walls, which was used to construct the cathedral's altar.

[5] Exposed metal bands were left protruding from the wall of the new transept, in preparation for completion of the cathedral in future generations.

[3] The expansion work was undertaken by builders A. T. Brine and Sons, and it was built from stone from the same quarry as the General Post Office building.

[10] In mid-1999, after a bequest of $2 million by the estate of Jim and Alice Hassell,[5] the archdiocese announced that it intended to finally complete the 1920s expansion; however construction was not expected to commence until 2001.

[14] In 2006, after the closure of the cathedral for construction, the remains of Perth's first bishops were found beneath floorboards in the aisle, marked only by a small cross carved in the boards.

[14] The remains of Perth's first bishop, John Brady, were exhumed in 2011 from his grave in France and a few months later he was laid to rest in the crypt of St Mary's Cathedral.

[5] Part of the restoration works involved hoisting the entire roof structure temporarily so that existing columns could be replaced and the walls reconfigured.

[17] The completed cathedral was officially opened by the Archbishop of Perth, Barry Hickey, on 8 December 2009 in a ceremony attended by the apostolic nuncio as well as Cardinal George Pell, 33 bishops and around 300 priests.