The Parish of Prince George, Winyah, was formed in 1721 from St. James, Santee, Parish. It was named for Prince George who became George II of England. The first building was in a bend in the Black River about twelve miles north of where Georgetown is now situated.

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As the rice planters became more numerous along the coast, the anticipated port of entry came closer to reality. The Parish was divided again in 1734. Since the original church fell within the newly established bounds of Prince Frederick's Parish, commissioners were appointed to build a new church for Prince George, Winyah, Parish in Georgetown. Bricks were collected as early as 1740, and the first record, who was sent by the English Society for the Propagation of the Gospel in Foreign Parts, held the initial service in Prince George on August 16, 1747.

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The church building was desecrated by enemy troops in both the Revolutionary War and the War Between the States. A gallery and the chancel were added about 1809 when repairs were made after the Revolution. The steeple was added in 1824.

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The box pews in the church were customary in colonial churches. Since there was no heating system available, pew owners frequently brought charcoal burners to their pews in cold weather. The box pews retained the heat.

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The stained glass window back of the altar is English stained glass, originally in St. Mary's Chapel at Hagley Plantation on the Waccamaw River. The chapel had been built by Plowden C. J. Weston for his slaves.