The Emperor of Rome has died and his sons Saturninus and Bassianus are squabbling over who will succeed him. The Tribune of the People, Marcus Andronicus, announces that the people's choice for new emperor is his brother, Titus Andronicus, a Roman general newly returned from ten years' campaigning against the empire's foes, the Goths. Titus enters Rome to much fanfare, bearing with him Tamora, Queen of the Goths, her sons, and Aaron the Moor. Titus feels a religious duty to sacrifice Tamora’s eldest son, Alarbus, in order to avenge his sons, dead from the war, and allow them to rest in peace. Tamora begs for the life of Alarbus, but Titus refuses her pleas. Tamora secretly plans a horrible revenge for Titus and all of his remaining sons.

Titus Andronicus refuses the throne in favour of the late emperor's eldest son Saturninus, much to Saturninus' delight. The two agree that Saturninus will marry Titus' daughter Lavinia. However, Bassianus was previously betrothed to the girl. Titus' surviving sons help them escape the marriage. In the fighting, Titus kills his son Mutius. Titus is angry with his sons because in his eyes they are disloyal to Rome. The new emperor, Saturninus, marries Tamora instead.

During a hunting party the next day, Tamora's lover, Aaron the Moor, meets Tamora's sons Chiron and Demetrius. The two are arguing over which should take sexual advantage of the newlywed Lavinia. They are easily persuaded by Aaron to ambush Bassianus and kill him in the presence of Tamora and Lavinia, in order to have their way with her. Lavinia begs Tamora to stop her sons, but Tamora refuses. Chiron and Demetrius throw Bassianus' body in a pit, as Aaron had directed them, then they take Lavinia away and rape her. To keep her from revealing what she has seen and endured, they cut out her tongue and her hands. This mutilation provides a source for black comedy throughout the play.

Aaron brings Titus' sons Martius and Quintus to the scene and frames them for the murder of Bassianus with a forged letter outlining their plan to kill him. Angry, the Emperor arrests them. Marcus then discovers Lavinia and takes her to her father. When she and Titus are reunited, he is overcome with grief. He and his remaining son Lucius have begged for the lives of Martius and Quintus, but the two are found guilty and are marched off to execution. Aaron enters, and falsely tells Titus, Lucius, and Marcus that the emperor will spare the prisoners if one of the three sacrifices a hand. Each demands the right to do so, but it is Titus who has Aaron cut off his (Titus') hand and take it to the emperor. In return, a messenger brings Titus the heads of his sons and his own severed hand. Desperate for revenge, Titus orders Lucius to flee Rome and raise an army among their former enemy, the Goths.

Later, Titus' grandson (Lucius' son), who has been helping Titus read to Lavinia, complains that she will not leave his book alone. In the book, she indicates to Titus and Marcus the story of Philomela, in which a similarly mute victim "wrote" the name of her wrongdoer. Marcus gives her a stick to hold with her mouth and stumps and she writes the names of her attackers in the dirt. Titus vows revenge. Feigning madness, he ties written prayers for justice to arrows and commands his kinsmen to aim them at the sky. Marcus directs the arrows to land inside the palace of Saturninus, who is enraged by this. He confronts the Andronici and orders the execution of a Clown who had delivered a further supplication from Titus.

Tamora delivers a mixed-race child, and the nurse can tell it must have been fathered by Aaron. Aaron kills the nurse and flees with the baby to save it from the Emperor's inevitable wrath. Later, Lucius, marching on Rome with an army, captures Aaron and threatens to hang the infant. To save the baby, Aaron reveals the entire plot to Lucius, relishing his retelling of every murder, rape, and dismemberment.

Tamora, convinced of Titus' madness, approaches him along with her two sons, dressed as the spirits of Revenge, Murder, and Rape. She tells Titus that she (as a supernatural spirit) will grant him revenge if he will convince Lucius to stop attacking Rome. Titus agrees, sending Marcus to invite Lucius to a feast. "Revenge" (Tamora) offers to invite the Emperor and Tamora, and is about to leave, but Titus insists that "Rape" and "Murder" (Chiron and Demetrius) stay with him. She agrees. When she is gone Titus' servants bind Chiron and Demetrius, and Titus cuts their throats, while Lavinia holds a basin in her stumps to catch their blood. He plans to cook them into a pie for their mother. This is the same revenge Procne took for the rape of her sister Philomela.

The next day, during the feast at his house, Titus asks Saturninus whether a father should kill his daughter if she has been raped. When the Emperor agrees, Titus then kills Lavinia and tells Saturninus what Tamora's sons had done. When the Emperor asks for Chiron and Demetrius, Titus reveals that they were in the pie Tamora has just been enjoying, and then kills Tamora. Saturninus kills Titus just as Lucius arrives, and Lucius kills Saturninus to avenge his father's death.

Lucius tells his family's story to the people and is proclaimed Emperor. He orders that Saturninus be given a proper burial, that Tamora's body be thrown to the wild beasts, and that Aaron be buried chest-deep and left to die of thirst and starvation. Aaron, however, is unrepentant to the end, proclaiming:

"If one good Deed in all my life I did,I do repent it from my very Soule."