St. Paul's, founded in 1822, was the first Roman Catholic parish in Upper Canada between Kingston and Windsor. It was hence the first Roman Catholic parish in York, which is now Toronto, and in the wide region beyond. It was built at the outskirts of the small but growing settlement of the present Toronto, which, for less than three decades, had clustered between Fort York, the waterfront, farmlands and the vast forest. From the outset St. Paul's has served a multicultural population, with a particular concern for the poor and for the education of their children. This first Catholic parish immediately founded the first Catholic school. Most of the early parishioners were Irish, although there were some French and Scottish people, and perhaps others, among them. From that time to the present, St. Paul's has served a highly diverse population, many of them immigrants from every part of the world who have come to Canada to build a new life.

When, in 1842, the Diocese of Toronto was separated from the Diocese of Kingston and became a separate entity, St. Paul's was the informal first Cathedral of the new diocese, being the seat of Bishop Michael Power until the 1848 completion of St. Michael's Cathedral. In 1889, the need for the expanding congregation prompted the expansion into the present Italian Renaissance-Style church.  It was designed by the Architect, Joseph Connelly, under the inspiration of the then Pastor Bishop Timothy O'Mahony. Its plan is patterned on that of the Major Basilica in Rome, St. Paul's Outside the Walls. In 1999, St. Paul's Church has undergone a much-needed process of restoration and refitting for continued service. 

On August 26 in the same year, Pope John Paul II conferred upon the church the title of a Minor Basilica, the first and only one in Toronto. The title of Minor Basilica indicates a tie with the Church of Rome and the Pope. To be so designated, a church must be, among other things, a centre of liturgical worship and pastoral work in the Archdiocese, and have a particular historical or other significance.