The earliest portion of the church dates from 1844. It was established by the Jesuits of St. Louis University for German Catholics residing near the college, then at Ninth Street and Washington Boulevard.

The cure of Ignatius Strecker, a parishioner at St. Joseph's, in 1864 was authenticated by the Vatican as one of the two miracles required for the canonization of St. Peter Claver. Because of this miracle, the church became known as the Shrine of St. Joseph.

Visitor's can view the church's Altar of Answered Prayers.