The play begins in Egypt, where one of Antony’s soldiers worries that Antony’s love for Cleopatra is excessive and has made him a weaker general. Cleopatra and Antony enter, and Cleopatra asks him how much he loves her. He says he cannot quantify his love for her. A messenger comes with news from Rome, but Antony disregards him, saying that he doesn’t care about Rome and is only concerned with Cleopatra. Antony and Cleopatra leave, and another of his soldiers notes how disrespectful Antony is toward the young Octavius, who sent the messenger.
Some of Cleopatra’s servants consult a soothsayer, who tells two of them that they will outlive Cleopatra herself. Cleopatra enters looking for Antony, but when he arrives, she gets annoyed with him and leaves. A messenger comes and tells Antony that his wife Fulvia has waged war against Octavius and Antony has lost territory in Asia minor, hinting that all this happened while Antony was neglecting his duties in Egypt with Cleopatra. Another messenger informs Antony that Fulvia has died. Antony says that he must “break off” from Cleopatra and his “Egyptian fetters.” He decides to leave Egypt for Rome, as he must help deal with Sextus Pompey, a rival of both Antony and Octavius who has been gaining power. He sends his advisor Enobarbus to make preparations for them to leave Egypt. Cleopatra sends a servant named Alexas to find Antony. She tells Alexas that if he seems happy, she should tell him Cleopatra is sad, and if he seems sad that she is happy. Antony tells Cleopatra that he must leave, and she is angry with him. She doubts his love for her and says that he is betraying her, but he tells her it is his duty to go to Rome. He promises her that the distance between them will not affect his love for her.
At Rome, Octavius complains to Lepidus about how Antony wastes time drinking and partying in Egypt. He says that Antony has become womanly because of his relationship with the manly Cleopatra. He wishes Antony would return, as Pompey is gaining power and becoming dangerous. Back in Egypt, Cleopatra passes time at her court with her servants and a eunuch named Mardian. She misses Antony and jokes that she is jealous of his horse, which gets to “bear the weight of Antony.” Alexas brings her a letter from Antony, along with a pearl. Cleopatra is happy to receive this sign of his affection and resolves to send him a letter every day.
Sextus Pompey discusses strategy with his followers Menas and Menecrates. He is confident that he will do well against Octavius, Lepidus, and Antony, because he thinks that Antony is still enjoying himself in Egypt, under control of “all the charms of love.” He is surprised to learn from a messenger that Antony has actually left Egypt for Rome. He tells Menas that Octavius and Antony, though not fond of each other, will be united as allies by their common enemy in Pompey. Antony arrives in Rome and Octavius chastises him for neglecting his duties and ignoring the messengers he has sent to Egypt. Lepidus tries to mediate between them, and Octavius’ adviser Maecenas urges them to forget their disagreements so that they can deal with Pompey. Agrippa, one of Octavius’ commanders, suggests that, now that Fulvia is dead, Antony could marry Octavius’ sister Octavia as a way of bringing Antony and Octavius closer together. Everyone agrees to the plan, and Octavius and Antony go to find Octavia. Enobarbus tells Agrippa and Maecenas about Antony’s wild times in Egypt and about Cleopatra’s seductive behavior. Octavius introduces Antony to Octavia, and he promises to be faithful to her. Antony talks with the soothsayer, who advises him to go back to Egypt. Antony makes plans to return to Egypt, and sends his man Ventidius to take care of some matters in Parthia. Lepidus, Maecenas, and Agrippa discuss their plans to meet and fight against Pompey. Back in Egypt, Cleopatra receives a messenger from Antony. She keeps interrupting him and hardly lets him speak, but he at last delivers his message, that Antony has married Octavia. Cleopatra is furious and takes out her anger on the messenger. She sends Alexas to go find Octavia and see what she looks like.
In Italy, Pompey meets with Octavius, Antony, and Lepidus to make a truce. The two sides agree upon terms and everyone goes to Pompey’s boat to celebrate with a feast. Menas tells Enobarbus he thinks the marriage between Antony and Octavia will keep Antony and Octavius together, but Enobarbus says he doubts it will. On Pompey’s boat, everyone drinks, and Lepidus gets so drunk he has to be carried off by servants. Menas whispers to Pompey that he could kill all his guests and take control of all of Rome, but Pompey says this would be dishonorable. Menas is annoyed that Pompey is not taking advantage of the situation, and decides to desert him. The feast continues and everyone drinks raucously, until Octavius says he has indulged in enough fun and departs.
Meanwhile, in Parthia, Ventidius wins a military victory for Antony. A soldier encourages him to pursue the fleeing Parthians, but Ventidius says he does not want to achieve too much for his rank and risk rivaling Antony’s authority. Back in Rome, Octavia weeps at having to leave her brother and go with Antony to Athens. Octavius sadly (but without crying) bids farewell to his sister. In Egypt, Cleopatra angrily hears about Octavia but is pleased to learn that Antony’s new wife does not rival her in beauty or excellence. At Antony’s house in Athens, Antony complains to Octavia about Octavius, who has begun speaking ill of him. Octavia says she will go to Rome to try to mend the rift between Antony and Octavius. Enobarbus talks with Antony’s follower Eros and tells him that Octavius has effectively defeated Pompey and pushed Lepidus out of power. Now, the world is divided between Antony and Octavius. In Rome, Octavius complains to Maecenas and Agrippa about Antony’s pompous behavior—among other things, he has declared Cleopatra the queen of Egypt and several other kingdoms. Octavia arrives and says that she has come to beg Octavius’ pardon on behalf of Antony, but Octavius informs her that Antony has gone back to Cleopatra in Egypt and betrayed her. He says Antony “hath given his empire / Up to a whore.”
Near the city of Actium, in Egypt, Antony and Cleopatra prepare for battle against Octavius. Cleopatra tells Enobarbus that she plans to go into battle with Antony, to Enobarbus’ dismay (he thinks a battle is no place for a woman). Against the advice of his commander Canidius, Antony decides to fight Octavius at sea. A soldier begs him to reconsider, but he remains stubborn. Canidius tells the soldier that Antony is now under Cleopatra’s control and they are nothing but “women’s men.” Elsewhere near Actium, Octavius gives orders to his general Taurus. Antony also prepares his forces for battle. Octavius’ and Antony’s navies fight a battle. They are evenly matched and there is no clear winner, but Cleopatra flees. Antony sees this and follows her, effectively conceding the battle. Canidius decides to desert Antony for Octavius, and Enobarbus remarks on how shameful and cowardly Antony’s behavior was, but Enobarbus decides to stand by his master. At Cleopatra’s palace, Antony is ashamed at having fled the battle. He is frustrated with Cleopatra and thinks that he will surrender to Octavius. He sends an ambassador to Octavius, who tells the ambassador that he will show no mercy to Antony, but will pardon Cleopatra if she will either kill Antony or drive him out of Egypt. Octavius sends a messenger named Thidias to go and promise Cleopatra gifts in an attempt to persuade her to leave Antony for Octavius. Antony is upset when he receives Octavius’ message, and plans to challenge him to a one-on-one duel. Enobarbus thinks this is a ridiculous plan and starts to wonder whether he should remain loyal to Antony. Thidias arrives and tells Cleopatra that Octavius will look kindly on her if she should leave Antony. Cleopatra tells him she will gladly surrender to Octavius. Antony enters and is furious when he sees Thidias kiss Cleopatra’s hand. He has servants beat Thidias and send him back to Octavius. He yells at Cleopatra for betraying him, but she convinces him that she is really faithful to him. Antony begins to recollect his courage and plans to fight back against Octavius. Enobarbus thinks that Antony is behaving very unreasonably and decides to abandon Antony to join Octavius’ forces. At Octavius’ camp, Octavius mocks Antony’s challenge of single-handed combat, and plans to defeat Antony once and for all. Antony learns of Octavius’ refusal to duel and plans to fight Octavius’ forces. He tells his followers to enjoy one last night of revelry and drinking before their final fight against Octavius.
Several soldiers in Cleopatra’s palace anxiously await the battle. They hear music coming from “under the earth,” and take this as a sign that Antony’s patron deity Hercules is deserting him. The next day, Antony prepares for battle and kisses Cleopatra before leaving. Antony learns from a soldier that Enobarbus has left him and joined Octavius’ forces. Antony orders for Enobarbus’ things to be sent after him with “gentle adieus and greetings.” Octavius prepares his troops for battle, deciding to put those who have deserted Antony’s side in the front lines, so that it will seems as if Antony’s forces are fighting themselves. Enobarbus receives his things from Antony, and regrets his decision to leave his kind former leader.
The battle begins, and Agrippa is forced to call for his forces to retreat. Antony has gained a victory, and returns to Alexandria to celebrate with Cleopatra. Meanwhile, at Octavius’ camp, Enobarbus dies full of regret for having betrayed Antony. The next day, Antony fights Octavius at sea. His soldier Scarus sees that swallows have built nests in Cleopatra’s sails, and is unsure of what this omen means. Antony’s fleet quickly surrenders to the forces of Octavius, and Antony is furious. He blames Cleopatra for the defeat and says that she has betrayed him. Cleopatra tries to soothe him, but he calls her a witch and sends her away. Charmian suggests to Cleopatra that she should go to her tomb, lock herself inside, pretend to kill herself, and send word of her death to Antony. Cleopatra agrees with the plan. Antony talks with Eros, and describes how sometimes clouds appear to be a particular shape, but then dissolve and change form. He says that he feels like these clouds and “cannot hold this visible shape.” He blames his defeat on Cleopatra, who he thinks betrayed him and didn’t truly love him. Mardian enters and tells Antony that Cleopatra really did love him. He says she killed herself and her dying word was Antony’s name. Antony says that he will follow Cleopatra’s example and kill himself. He tells Eros to stab him, but Eros refuses and stabs himself instead. Antony then stabs himself. One of Cleopatra’s servants enters and tells Antony that Cleopatra is not really dead. Antony is carried to Cleopatra’s tomb.
Antony arrives at Cleopatra’s tomb, and Cleopatra is distressed to see him dying. He tells her to seek safety with Octavius, but she refuses and promises to end her own life and not become Octavius’ prisoner. Antony dies and Cleopatra orders for him to be buried “after the high Roman fashion.” At his camp, Octavius plans to send a messenger to get Antony to surrender, but receives news of Antony’s death. He is saddened by the news, as he respected Antony as a strong opponent. Octavius sends his men Proculeius and Gallus to go to Cleopatra and persuade her that he has no ill intentions toward her, so that she will not commit suicide like Antony and ruin his actual plans to parade her as a prisoner in his triumph at Rome. At her tomb, Cleopatra, resolves to end her own life, but then Proculeius and Gallus arrive and tell her not to worry about her treatment at Octavius’ hands. Proculeius and Gallus leave, and Octavius’ follower Dolabella enters. Cleopatra tells Dolabella about a dream she had of a gigantic, powerful Antony who ruled the world. Dolabella takes pity on her and admits to her Octavius’ actual intentions. Octavius arrives and tells Cleopatra that he will not harm her if she surrenders to him. He leaves, and Cleopatra thinks about how she would become a subject of public ridicule at Rome. She sends Charmian and her servant Iras to get her best clothes and crown, so that she can look her most beautiful when she dies.
A common man arrives, bearing a basket of figs for Cleopatra. Hidden in the basket are asps (poisonous snakes). Cleopatra kisses Charmian and Iras goodbye, and Iras falls dead. Cleopatra takes an asp and lets it bite her breast, then has another one bite her arm. She dies. A guard rushes in and sees what has happened, as Charmian lets an asp bite her and dies, as well. Octavius enters and, while disappointed at what has happened, calls Cleopatra “bravest at the last.” He orders for Cleopatra to be buried with Antony and says that his army will attend a funeral for Antony and Cleopatra before returning victorious to Rome.