In 1774, the colonies where positioning themselves for independence from Britain. Arthur and his father Henry chose liberty and sided with their fellow colonists. He took a firm and decided stand in opposition to British encroachment and oppression.<ref>[http://virtualology.com/arthurmiddleton.org/ Arthur Middleton, Virtuology.org]</ref> Arthur headed the Charleston Council of Safety in 1775 and in 1776, he filled the seat his father occupied in the Second Continental Congress. He continued as a member of Congress, residing with his family, who had accompanied him at the close of 1777.
In 1779, the British invaded the southern colonies. Middleton fought to defend Charleston. The British took Charleston and Middleton was captured. He was taken prisoner by Sir Henry Clinton and sent to St. Mark's Castle in St. Augustine as a prisoner. Together with [[Thomas Heyward Jr.]] and [[Edward Rutledge]], Arthur languished over a year before being traded in a prisoner swap. He returned to find all his property looted; the buildings were left standing, but all his wealth was destroyed.
Middleton reunited with his family after completing his term in Congress 1782. He declined his seat in Congress after the war, preferring to spend retirement with his family.