[4] Established in 1826 to serve Irish immigrants living in the neighborhood, it is the third oldest Catholic parish in New York.

The original portion is the second-oldest Roman Catholic structure in the city, after St. Patrick's Old Cathedral, which was built in 1815.

In 1831, anti-Catholic nativists set fire to the church, but it was not completely destroyed and continued to operate.

The first New York chapter of the Ancient Order of Hibernians was established in 1836 at nearby St. James Church partly in response.

[7] Charles Edward McDonnell, future Bishop of Brooklyn, was assigned as curate here in the autumn of 1878.