He was educated in England, at Hackney and Trinity Hall, Cambridge. 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 1764 Arthur and his bride Mary Izard settled at Middleton Place. Keenly interested in Carolina politics, Arthur Middleton was a more radical thinker than his father Henry Middleton. He was a leader of the American Party in Carolina and one of the boldest members of the Council of Safety and its Secret Committee. In 1776, Arthur was elected to succeed his father in the Continental Congress and subsequently was a signer of the Declaration of Independence. Despite the time he spent in England, his attitude toward Loyalists was said to be ruthless.
During the American Revolutionary War, Arthur served in the defense of Charleston. 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, until exchanged in July the following year. Arthur died on January 1, 1787 at the age of 44. He was buried in the family tomb in the Gardens at Middleton Place. The plantation then passed to Henry, his eldest son. His son, Henry went on to a career in politics. He was elected Governor of South Carolina (1810-1812), U.S. Representative (1815-1819), and Minister to Russia (1820-1830).