One of the largest plantation owners in South Carolina, Middleton's career included serving as a justice of the peace, a member of the Commons House of Assembly, speaker of Commons House of Assembly, and as a member of the provincial council.
In 1770 he resigned from the provincial council over disagreements with British policy and in 1774 was selected as a delegate to the Continental Congress.
He was, however, not in favor of independence and resigned from the Second Continental Congress in February of 1776. He also accepted a return to the status of a British subject in 1780 after being captured when the British took Charlseton, although he reverted again after the revolutionaries won the war after all.
He was the father of Arthur Middleton, who took his seat in the Second Continental Congress and was one of the signers of the Declaration of Independence.
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