In 1459, Margaret outlawed the Yorkist leaders, and in December 1460, she killed Richard, the Duke of York, and vengefully displayed his head, adorned with a paper crown, outside of York.

On February 3, 1461, Edward IV, son of the Duke of York, defeated the Lancastrian forces at Mortimer's Cross in Herefordshire. Margaret and her son, Prince Edward, recruited a large army, and then on February 17, 1461, they defeated the Yorkists at the second Battle of St. Albans. Margaret of Anjou freed her husband. However, Edward IV usurped the throne on March 4 and defeated Margaret's army at the Battle of Towton, Yorkshire, on March 29. It was then that Margaret's small family of three fled to Scotland.

Later, in France in 1570, Margaret became reunited with Warwick, who was her former Yorkist enemy. However, Margaret was in for a surprise. Warwick was actually planning to overthrow Edward IV and restore Lancastrian Henry VI to the throne. Margaret, undoubtedly suspicious, didn't want him for an ally, but her desire to restore Lancastrian authority was immense, so she reluctantly agreed to his help. Warwick's plan was successfully executed in October 1470. However, Margaret didn't return to England until April 14, 1471 -- the same day that Warwick was killed in battle against Edward IV. Margaret was defeated at Tewkesbury in May by Edward IV, and her son was killed. Shortly after, her husband was captured and imprisoned in the Tower of London, where he was ultimately killed by order of Edward IV. Margaret remained in custody in England until she was ransomed by the French king Louis XI in 1475. She then returned to France, where she spent her last years in poverty. She died in 1482 and was buried in Angers Cathedral at Chateau Dampiere.