William was son of a senior Sir William Brandon of Soham Court, Suffolk (1425-1491) and Elizabeth, daughter and co-heiress of Sir Robert Wingfield. He married Elizabeth, daughter of Sir Henry Bruyn and Elizabeth, widow of Sir Robert Darcy, with whom he had five children:
In 1478 Sir John Paston wrote that "young William Brandon is in ward for the rape of a widow."
Brandon was one of the key London connections behind the Buckingham Revolt of 1483, along with his brother Thomas and brother-in-law, Wingfield.
Pardoned in March 1484 he seized a ship at Mersea and sailed for France where he was joined by his wife who gave birth to their eldest son in Paris.
He joined his brother Thomas in the relief of the Hammes fortress and both were knighted by Henry Tudor when he landed at Milford in 1485. Brandon was the only notable victim in Henry's army at Bosworth, being killed by King Richard III while carrying Henry's royal standard.