The congregation was co-founded with Charles Towne, 1680–1685, by the English Congregationalists, Scots Presbyterians, and French Huguenots of the original settlement.

The earliest records of the church were lost when a hurricane swept them from the manse, located at White Point (the Battery), in 1713.

While many Presbyterians remained, the policy of this church "was not so much to define exactly a particular mode of their discipline, and to bind their hands up to any one stiff form adopted either by Presbyterians, Congregationalists, or Independents, as to be upon a broad dissenting bottom, and to leave ourselves as free as possible from any foreign shackles, that no moderate persons of either denomination might be afraid to join them.

Prominent members of the Meeting House, and its distinguished minister, William Tennent (1772–1777), were frequently heard speaking for political and religious freedom.

Tennent took his life in his hands when he made a wide tour of the Carolina back-country in 1775 to gain subscribers for the cause of independence.

Noteworthy is the fact that Palmer was a special son of this church, born in Philadelphia just two weeks after his parents had been driven into exile there in 1781.

When the British occupied the city, the church was bitterly rewarded for its love of freedom by the illegal exile of 38 heads of families to prisons in St. Augustine and then to Philadelphia.

The Meeting House, vacant since the cannonball episode, was used as a British hospital[4] and/or a warehouse, with the pews destroyed and the building suffering other damage.

Hollinshead and Keith, co-pastors of the church, preached one sermon in both houses each Sunday, alternating morning and afternoon services.

Martha Laurens Ramsay proposed a circular form, and Robert Mills, Charleston's leading architect who also designed the Washington Monument, completed the plans.

[6] The people of Circular Church, as it was now popularly called, stopped the laughter in 1838 by raising a New England–style steeple that towered 182 feet (55 m) above Meeting Street.

The current church building was built in the Richardsonian Romanesque beginning in 1890 (the third on its site), to plans by Stephenson & Greene of New York.