The figure of the Prologue comes onto the stage to declare that what follows is a serious play. Several lords, including Buckingham, enter; Buckingham is angry that Cardinal Wolsey has such powerful influence over the king. Buckingham suspects Wolsey of being ambitious and disloyal. The other lords urge him to keep his words to himself, but just then, a guard comes to arrest Buckingham with the charge of treason. He goes quietly to jail.

The king and queen attend a hearing in which Wolsey questions Buckingham's former employee (the Surveyor) about his loyalties. This man declares that Buckingham fancied himself next in line to the throne should the king die without an heir. Henry is angered and sentences Buckingham to death for disloyalty. However, the queen thinks that the Surveyor bears a grudge against Buckingham and has delivered lies in his testimony.

Many lords go to a dinner party at Wolsey's house, and the king comes in disguise. Wolsey sees through the disguise, and the king meets Anne Bullen. He is very impressed with her beauty.

Several men in the street discuss the trial of Buckingham, how he defended himself eloquently but was sentenced to death. The common people hate Wolsey, they all agree. Buckingham, speaks to the people, forgiving those who turned against him. He notes how his own death resembles that of his father, who also was killed by the king to whom he was loyal all his life.

Several lords hear talk of the king's plan to divorce his wife, Katharine. Anne hears the news, too, and is sorry for Katharine, reflecting that she herself would never want to be the queen. Then, she receives a new title and money from the king, as a sign of his fondness for her.

A cardinal from Rome arrives with the Pope's decision about whether Henry may divorce Katharine. Katharine beseeches the king not to divorce her, saying that she has been a loyal and honest wife to him for two decades. She calls Wolsey a traitor and refuses to submit to his will, sweeping out of the court. The king enumerates his reasons for believing his marriage to Katharine is unlawful and must be dissolved. Wolsey and the cardinal from Rome speak to Katharine, trying to convince her to go along with the divorce so she may stay under the king's care. She curses them for their role in her demise, which enrages her after so much faithfulness.

The lords of the court now suspect Wolsey has been double-dealing in the divorce. But before they can work out a scheme to bring him down, Wolsey falls through his own inattention. The king intercepts an inventory of the possessions Wolsey has seized from fallen lords and a letter Wolsey wrote to the Pope urging the Pope to refuse the divorce request until Henry forgets his infatuation with Anne. The king confronts him and asks Wolsey if he has been a good servant, and Wolsey replies affirmatively. Then, the king shows him the papers he has uncovered. Wolsey knows he is lost. The lords deliver the king's charges against Wolsey, stripping him of his title and belongings. Wolsey regrets his ambitious behavior and sees that he was wrong to have tried to influence the affairs of state. Saying that he finally knows himself, he leaves the court.

The king announces his marriage with Anne, and people in the street scramble to watch the procession to her coronation. Katharine has now been demoted to "Princess Dowager," and she expects that her demise will lead soon to her death. Hearing of the death of Wolsey, she speaks against him again, but one of her attendants (Griffith) praises him. Katharine is, thus, convinced to forgive Wolsey.

In the court, the lords hear that the queen (Anne) is in labor. The king discovers a plot against his recently returned friend Cranmer, so he summons Cranmer to explain the complaints against him. Cranmer is convinced that he will fall into traps set for him, so the king gives him his ring as a sign of his support. Meanwhile, Anne gives birth to a female child.

Cranmer is called before the Council, of which he is a member, to answer to complaints against him. The king watches the proceedings from above. The lords tell Cranmer that nothing can be done about the complaints while he is a Council member, so they want to make him into a regular citizen by confining him to the Tower. When guards arrives to take him away, Cranmer shows the lords the king's ring, and the king enters the Council to scold the lords for infighting, urging them to get along with each other. Cranmer forgives those who have plotted against him, specifically Gardiner.

Commoners gather in the street to view the baptism of the king's daughter. Cranmer baptizes her as Elizabeth and speaks of her future greatness and the achievements both she and her successors will have. The Epilogue comes on stage, urging the audience to applaud.