Enthralled by his love for the beautiful and captivating Cleopatra, Mark Antony languishes at the courts of Egypt, totally neglecting his political and military duties as a member of Rome’s ruling triumvirate. He learns that Octavius is angry at his conduct and that his own wife, Fulvia, has gone to battle against Octavius and is now dead. Antony resolves to leave Cleopatra and return to Rome. Enobarbus, Antony’s friend and lieutenant, warns him that Cleopatra will resist his leaving. Just as predicted, she flies into a rage but is eventually reconciled to Antony’s departure.

In Rome, Octavius and Lepidus anxiously await Antony’s return. Pompey, the son of Julius Caesar’s old rival, is in rebellion against Rome and has gained control of the sea.

Pompey, in Messina, hopes that there will be no reconciliation between Octavius and Antony, who have met in Rome on less than friendly terms. Lepidus sees a way to reconcile them by suggesting that Antony marry Octavia, Octavius’s sister, and Antony agrees. Regaining military control, Antony sends a force to fight the rebellious Pompey and his army.

Cleopatra flies into a rage when she learns of Antony’s marriage and beats the messenger before being overcome by despair. In Messina, Antony, Octavius, and Lepidus meet with Pompey to work out a treaty, which is then sealed with a drunken feast.

Antony and his new wife, Octavia, leave for a new home in Athens, and Cleopatra takes heart in the news that Octavia is no match for her.

The reconciliation between the triumvirs is not of long duration. Octavius is soon at odds with Antony, and when Octavia leaves for Rome to intercede in her husband’s behalf, Antony returns to Cleopatra. In the meantime, Octavius has arrested Lepidus on charges of conspiracy.

War between Antony and Caesar begins in earnest; and, over Enobarbus’s objections, Cleopatra joins her fleet in the battle, which Antony stubbornly insists on fighting by sea. Cleopatra suddenly retreats, Antony follows, and the battle is lost. Humiliated, Antony rages that he has relinquished his honor as a soldier in favor of Cleopatra’s love. He sends a message to Octavius offering to surrender in return for permission to live peacefully in Athens and for assurance that Cleopatra will remain queen of Egypt. Octavius refuses, and Antony, in his frustration, challenges him to single combat. Enraged at finding Octavius’s emissary kissing Cleopatra’s hand, Antony has the emissary whipped.

Preparations are made for another battle and the next morning Antony learns that his beloved lieutenant Enobarbus has deserted him. In a loving gesture, Antony sends Enobarbus’s treasure to him in Octavius’s camp. Learning of this, Enobarbus vows not to join in the battle against Antony.

Fighting this time on land, Antony wins handily. The guilt-stricken Enobarbus commits suicide.

The next day, the battle at sea is lost, and Cleopatra’s navy surrenders. Cleopatra, terrified of Antony’s fury, takes refuge in a tomb, having word sent to Antony that she has died. Antony, choosing to join her in death, falls on his sword. Mortally wounded, he learns that Cleopatra is not dead. He is taken to the tomb where he dies in her arms.

Octavius resolves to give Antony a hero’s funeral. He sends word to Cleopatra that she has nothing to fear, but secretly he intends to display her in Rome as his captive. Learning of this, Cleopatra has poisonous snakes smuggled into her. Dressed in her most royal garments to meet Antony, she dies.