Margaret was born in the province of Lorraine in France, the daughter of Rene I of Naples, Duke of Anjou, King of Naples and Sicily. She married King Henry VI, who was eight years her senior, on April 23, 1445, at Titchfield in Hampshire.
Henry, who had more interest in religion and learning than in military matters, was not a successful king. He had reigned since he was a few months old and his actions had been controlled by regents. When he married Margaret, his mental condition was already unstable, and by the time their only son, Edward of Westminster, was born, on October 13, 1453, he had suffered a complete mental breakdown. Rumours were rife that he was incapable of fathering a child and that the new Prince of Wales was the result of an adulterous liaison on Margaret's part.
Margaret seems to have been quite mild-mannered until her husband was deposed, on March 4, 1461, by a rival claimant to the throne, Edward IV of England. She was determined to win back her son's inheritance, and fled with him into Wales and later Scotland, where she was assisted by Henry's half-brother, Jasper Tudor. Finding her way to France, she made an ally of King Louis XI of France, and at his instigation she allowed an approach from Edward's former supporter, Richard Neville, Earl of Warwick, who had fallen out with his former friend and was now seeking revenge for the loss of his political influence. Warwick's daughter, Anne Neville, was married to Margaret's son, Edward, Prince of Wales, in order to cement the alliance, and Margaret insisted that Warwick return to England to prove himself, before she followed. He did so, restoring Henry VI briefly to the throne towards the end of 1470.
By the time Margaret, her son and daughter-in-law were ready to follow Warwick back to England, however, he had been defeated and killed by the returning King Edward IV, and Margaret was forced to lead her own army at the Battle of Tewkesbury in 1471, at which they were defeated and her son was killed. Over the previous ten years, she had gained a reputation for aggression and ruthlessness, but now she was a broken spirit, imprisoned in the Tower of London until ransomed by the French king. She died on August 25, 1482, in Anjou, where she was buried.