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St. Mary of the Annunciation Catholic Church is home to the oldest Catholic parish in the southeastern United States. Founded in 1789, it was the mother parish to other Catholic congregations in Georgia and the Carolinas. The building itself is also significant. It was erected in 1839 in the Greek Revival style and features a portico with four large Doric columns supporting an entablature, a parapet wall with a large cross in the center, and arched and circular windows with keystones above the main entrance. The church was added to the National Register of Historic Places in 1976.

St. Mary of the Annunciation Catholic Church was established in 1789, making it the oldest Catholic parish in the southeastern United States..

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It is believed that the first Catholic mass in Charleston was held in 1786 by an Italian priest who had been a ship bound for South America. The ship stopped in Charleston to avoid bad weather. At the time, there were few Catholics in the city; the vast majority of the residents were Protestant. The mass took place in the house of an Irish Catholic and only around 12 people attended. Two years later, an Irish priest from the Diocese of Dublin, Ireland arrived and rented a small wood-frame building. After he departed Charleston due to health issues, another priest, Rev. Thomas Keating, arrived in 1789. Keating bought the church property and named the parish St. Mary of the Annunciation. He, too, became ill and left within three years (he died in Philadelphia).

By 1790, the congregation had grown to almost 200 members. Many were refugees fleeing from a slave uprising (what is now known as the Haitian Revolution) in the French colony of Santo Domingo. These include the children of French naval officer Admiral de Grasse, who blockaded British General Lord Cornwallis at the Battle of Yorktown in the fall of 1781.

Construction of the second church building, a brick structure, was completed in December 1806. It was lost in the April 1838 fire that destroyed two-thirds of Charleston (the Jewish temple across the street was also destroyed). However, the present church was built and opened in June 1839. During the Civil War, a number of shells hit the church and gravestones in the adjacent graveyard. St. Mary later survived an earthquake in 1886 and hurricanes in 1893 and 1989.

McNulty, Katharine N. "St. Mary's Roman Catholic Church." National Park Service - National Register of Historic Places Nomination Form. November 7, 1976. https://npgallery.nps.gov/GetAsset/f5a35599-7aee-40fb-91e3-69fe1797035c.

"Our History." St. Mary of the Annunciation. Accessed April 15, 2021. http://www.sma.church/our-history.html.