The story of Our Lady of Perpetual Help begins on the corner of Prospect and Maple Streets in 1890, the site of today’s Mater Dolorosa school. Over two years, at a cost of $79,000, a chapel, rectory, convent, and school were built on that site. An historically French Catholic parish, it was initially known as the Church of Notre Dame Du Perpetual Secours. Its growing congregation led church leaders to purchase a tract of land on Chestnut Street for a larger building in 1917. Designed by Louis Caron and built in the Byzantine Revival style, reminiscent of early French churches in Quebec, construction of the church began in April of 1922 and the dedication took place in October, 1923.

The community grew steadily, adding a school and rectory in 1927. The school's student enrollment rose to 400 in the 1910s and remained consistently high into the 20s and 30s. It occupied a large footprint along Chestnut Street and rented out buildings to local charities, including Kate’s Kitchen. In 1973, the congregation launched a 50th anniversary fundraising drive to renovate the church interior, with a goal of raising $180,000. In a creative twist, this included the sale of gold, silver, and bronze-plated commemorative coins that were available to buy after masses and cost $50, $10, and $2 respectively. On August 29, 1999, shortly after celebrating its 77th anniversary, the church succumbed to a fire that was set in a neighboring apartment building. In the end, the fire spread to 12 buildings and leveled the city block.