After the death of the Holy Roman Emperor Charles V, his son, King Philip II of Spain, went to war with France and occupied Flanders (present day Belgium). To forge a peace, Philip has betrothed his son, Don Carlos, to Elisabeth of Valois, daughter of the King of France.
Act I
At Fontainebleau, the peasants lament their suffering caused by the Spanish war. They turn to the compassionate Elisabeth, in the hope that her upcoming marriage to Don Carlos will bring peace. Carlos, unrecognized, sees Elisabeth with her page, Thibault. He is enraptured by her beauty. When they meet, he misleads her about his true identity, and she asks him about her betrothed. Carlos shows her a portrait of himself, and she realizes that he is her fiance. The two express their love, but the Count of Lerme interrupts them, announc-ing that Philip now requests Elisabeth's hand for himself. Carlos is shocked, but Elisabeth sorrowfully accepts her betrothal to Carlos's father to bring her people peace.
Act II
Before Charles V's tomb near Madrid, the trembling Carlos believes he recognizes the voice of his dead grandfather. Rodrigue, the Marquis of Posa, finds Carlos and urges him to support Flanders against Spain. Carlos admits to Posa his secret love for Elisabeth, who is now Queen, and the pair vows fraternity while Philip and Elisabeth arrive at the chapel to pray.
In the chapel garden, Princess Eboli, who secretly loves Carlos, entertains the ladies-in-waiting. Meanwhile, Posa arranges for Elisabeth to meet Carlos alone. Carlos begs Elisabeth to have Philip send him away to Flanders, but his passions overwhelm him. In desperation, Elisabeth tries to make Carlos understand the impossibility of their love, and Carlos flees in terror. Philip enters with his full retinue and is angered at finding Elisabeth alone. He proceeds to banish her attendant, the Countess of Aremberg. Elisabeth consoles the Countess, her only friend, with a nostalgic lament. All depart except Philip, who detains Posa, whose honesty intrigues him. Posa elo¬quently urges Philip to feel compassion for the oppressed people of Flanders. Philip defends his policies as King but personally admits doubts. He suspects a treacherous love between his son and Elisabeth and tells Posa to watch over them. As he departs, he warns Rodrigue of the Grand Inquisitor.
Act III
At the palace, Carlos mistakes Eboli¬who has agreed to take Elisabeth's place at the ball and so is wearing Elisabeth's veil— for Elisabeth. Eboli has sent Carlos an unsigned invitation to meet at midnight. When they meet in the garden, he mistakes her for Elisabeth, and so Eboli discovers that Elisabeth is Carlos's true love and vows vengeance. Meanwhile, to protect Carlos, Posa asks him for any incriminating documents about the Flemish insurgency, and Carlos decides to trust his friend.
In the Cathedral square, the people await the auto-da-fe—a public burning of heretics. A Royal Herald announces the King, but deputies from Flanders interrupt the ceremony and implore Philip to spare their homeland. The crowd feels pity, but the monks urge condemnation. Carlos demands that his father make him regent of Flanders. When he receives no response, he threatens him with a sword. Posa, to Carlos's surprise, disarms him and receives an honor from Philip for doing so. The heretics burn as Carlos is imprisoned, and a divine voice offers salvation to the dying victims.
Act IV
In his private study, King Philip gloomily meditates. The Grand Inquisitor agrees to Philip's desire to kill Carlos, but the priest demands the death of Posa as well and threatens the King into submission. Having discovered the portrait of Carlos in Elisabeth's jewelry box, snatched for him by the vengeful Eboli, Philip confronts his wife. She faints, and he calls for assistance. Eboli, when alone with the Queen, in remorse confesses both her betrayal of Elisabeth and her own adultery with Philip. Elisabeth banishes her. Eboli curses her own beauty and resolves to save Carlos.
Posa, willing to let Carlos's incriminat¬ing papers be found on himself, bids farewell to Carlos in prison. Posa urges Carlos to save Flanders. Posa is shot in the back by the Inquisition and dies. Eboli leads a public uprising, which storms the prison, intent on freeing Carlos. The Grand Inquisitor's command stills the crowd, but Carlos escapes.
Act V
Elisabeth prays at the tomb of Charles V. Carlos meets her there and vows to save Flanders. They now both accept the importance of their duties over their love for each other. Philip and the Inquisitor surprise them, arrest Carlos, and condemn him to death. Suddenly the monk who resembles Charles V mysteriously appears and takes Carlos into the depths of the cloister.