The play begins with a confrontation between Richard, Duke of York (the future King Richard III), the reigning King Henry VI and their respective supporters. Threatened with physical violence by the Earl of Warwick (Richard Neville), the king brokers a deal to make York his heir. Disgusted at his cowardice, his supporters abandon him. The Queen, Margaret of Anjou, makes it clear that she will not agree to this, and declares war on the Yorkists, with the assistance of the young Lord Clifford and other supporters, including her son, Edward, Prince of Wales.

The Third Part of King Henry VI, brings Shakespeare's story of Henry's reign and fall to Richard, Duke of Gloucester, to its unhappy close.