Established in the mid-1860s by German and Irish immigrants, this parish in the Baden area of St. Louis was served by German-born priests until 1976. In 1873, English-speaking members of the parish formed a separate congregation, Our Lady of Mount Carmel. The two parishes merged and were renamed Our Lady of the Holy Cross in 1993. The congregation gained national attention between 1940 and 1976 when its pastor, Monsignor Martin B. Hellriegel (1890-1981), became a leader in liturgical reform within the Catholic church.

The red brick Gothic Revival church was completed in 1909. It was designed by a collaboration of architects: Ruedell & Odenthal of Cologne, Germany; St. Louis architect/sculptor Joseph Conradi and Father Peter Wigger of Holy Cross.