Organized in 1839 and named for St. John's, Berkeley Parish, this was the third Episcopal church established north of Columbia. The Rev. Josiah Obear became its first rector in 1841, serving 1841-49 and 1875-82. The first sanctuary, a wood-frame building, was built on Fairfield St. in 1842. During the Civil War many families who fled the lowcountry and lived in Winnsboro as refugees worshipped at St. John's.
The original sanctuary was burned by Union troops in February 1865. A second wood-frame sanctuary was designed by a former St. John's rector, the Rev. John DeWitt McCullough, in the Carpenter Gothic style. It was built on Liberty St. in 1869 and burned in 1888. This brick sanctuary, designed by architect R.S. Schuyler in the Gothic style and constructed by contractor George Waring, was consecrated in 1889.