[1] He studied law at the Middle Temple and traveled extensively in Europe where his taste in literature, music, and art was developed and refined.

In 1776, Middleton was elected to succeed his father in the Continental Congress and subsequently was a signer of the United States Declaration of Independence.

After the city's fall to the British in 1780, he was sent as a prisoner of war to St. Augustine, Florida (along with Edward Rutledge and Thomas Heyward Jr.), until exchanged in July the following year.

[4] The death notice from the State Gazette of South-Carolina describes him as a "tender husband and parent, humane master, steady unshaken patriot, the gentleman, and the scholar."

The plantation passed to Henry, his eldest son, later governor of South Carolina, U.S. Representative and minister to Russia.