This opera about Anne Boleyn is one of three Donizetti wrote based on English Tudor history, along with Roberto Devereux (the assumed lover of Elizabeth I) and Maria Stuarda (about Mary, Queen of Scots). The main characters of these operas are referred to as the three Donizetti Queens.

The work opens with Anna as the unhappy, ignored wife of Henry VIII. She knows how important it is to give Henry a male heir as soon as possible but in the three years they have been married, she has had only one daughter (the future Elizabeth I) and several miscarriages. Soon she learns the king has transferred his affections to one of her ladies-in-waiting, Jane Seymour.