[6] The parish was established in June 1885 and Father Patrick Fay, the chaplain to Canadian Pacific Railway (CPR) workers, was chosen as pastor.

In order to pick a site for the new church, legend has it that Father Fay went to the Coal Harbour waterfront, looked south towards the forested land (present-day Downtown Vancouver) and chose the area that contained the tallest tree.

[8] At the time it was finished, the building was praised as "the finest piece of architecture west of Toronto and north of San Francisco.

"[15][16][17] The new Church of Our Lady of the Holy Rosary opened on December 8, 1900 – the Feast of the Immaculate Conception[7] – and was blessed one day later by Archbishop Alexander Christie of Portland, Oregon.

[18] The OMI – which administered the parish since 1893 – eventually left in 1927 after difficulties arose from the mortgage agreement that had helped pay for the construction of the cathedral.

The ceremony – which commenced just after daybreak – was officiated by the Archbishop of Vancouver William M. Duke, with the subsequent solemn pontifical Mass celebrated by Michael Harrington, the Bishop of Kamloops.

[22] On October 7, 1952, the feast day of the cathedral's namesake, a gunman entered the church and fired a round from his rifle at the altar.

[23] A minor tilt in the bell tower of the cathedral was detected in April 1959, probably due to the drilling and blasting of a nearby tunnel.

[9] In late September 2001, the cathedral became the first place in Canada to host the relics of Saint Thérèse of Lisieux during her reliquary's three-month-long tour of the country.

[27] Over the years, several notable people had their funeral requiem mass said at the cathedral, including beloved local lifeguard and swim instructor Joe Fortes (1922),[28] Chief Dan George of the Tsleil-Waututh Nation (1981),[29] and former Vancouver police commissioner William Cameron Murphy in 1961.

In late 1932, the "tin scales" that covered spire of the taller steeple were cleaned and repaired, and the cross atop of it was repainted.

[14] When the cathedral was first built, seven bells – representing the sacraments – were cast at the Fonderie Paccard in Annecy-le-Vieux, Savoy, France and were blessed on October 21, 1900.

[9][39][40] They are one of the few peal of bells hung in the English style found in North America,[41] and one of three in British Columbia – the others are located at Westminster Abbey in Mission and Victoria's Christ Church Cathedral.

[16][43] Over the years, the instrument's condition deteriorated due to "general wear and tear",[43] shoddy repairs and water damage caused by the leaking roof.

[45] A copy of the bronze sculpture Homeless Jesus by Canadian artist Timothy Schmalz was installed in front of the cathedral in the spring of 2017.

[46][47] According to Stanley Galvon, the rector at the time, the statue is intended to be "a catalyst to make people think about" the city's homelessness crisis.

They ordered the Church to "get off native land" and demanded that they disclose the burial locations of children who died in residential schools.

[52] This came as a result of the Archdiocese suspending all public masses starting from March 21 onwards, in response to the 2019–20 coronavirus pandemic.