Charles's grandfather was the exiled Roman Catholic king James II (ruled 1685–88), and his father, James Edward, the Old Pretender, affected in exile the title King James III. Charles was reared a Catholic and trained in the arts of war. In 1744, during the War of the Austrian Succession (Austrian Succession, War of the) (1740–48), he joined a vast French fleet that was torn apart by a storm before it could invade England.

Unable to obtain more French aid, Charles decided to set off on his own to regain the crown. He landed with a tiny force of about a dozen men on the west coast of Scotland in July 1745 and raised the Highlands in revolt. On September 17, with about 2,400 men, he entered Edinburgh. Four days later he routed Sir John Cope's army at Prestonpans, near Edinburgh; early in November, with 5,500 men, he crossed the English border and headed toward London. Charles advanced as far as Derby before his officers, discouraged by lack of French and English support and frightened by the prospect of facing 30,000 government troops, forced him to retreat into Scotland. His troops melted away, and on April 16, 1746, William Augustus, duke of Cumberland, decisively defeated him at Culloden Moor, Inverness-shire. For the next five months Charles was relentlessly pursued by British soldiers. Finally, helped by loyal supporters (in particular, Flora Macdonald (Macdonald, Flora), he escaped by ship to France (September 1746).

Charles wandered around Europe trying to revive his cause, but his drunken, debauched behaviour alienated his friends. After he settled in Italy in 1766 the major Roman Catholic powers repudiated his title to the British throne. Romanticized through ballads and legends, “Bonnie Prince Charlie” became a national hero of Scotland.