The film begins in Alexandria with Cleopatra VII, Egypt's rightful Queen, in exile, while her sister Arsinoe and brother, Ptolemy have stolen the throne. Roman general Julius Caesar comes to collect Egypt's tax debt. After conversing with a courtesan, Cleopatra smuggles herself into the palace wrapped in a carpet; a gift from her to Caesar. He accepts the gift and the young queen is revealed to Caesar. The two spend the night together, and the next morning, Cleopatra and Ptolemy are betrothed to marry by Caesar. Shortly after the siblings are wed, Cleopatra is proclaimed Queen of Egypt, forcing Ptolemy to join forces with Arsinoe and drive their sister out of Alexandria.
A war breaks out between the Romans and Ptolemy's Egyptian forces, and in the process, Alexandria's great library is burned to the ground. Even with this loss, Cleopatra soon celebrates the return of her Roman lover, the death of her brother, and the capture of her traitor sister. The two take a 2-month journey down the Nile aboard one of the Queen's elegant ships. Upon their return, Caesar breaks the news that he must leave for Rome. Unbeknownst to him, Caesar leaves Cleopatra pregnant with his child. A son is born to the queen roughly nine months later; he is named Caesarion, in honor of his father.
Back in Rome, believing that he should hold the same status as his Egyptian lover, Caesar demands he be declared King of Rome. Although they are hesitant to do so, the senate eventually grants Caesar's request. Now having been declared king, Caesar invites Cleopatra to stay at one of his villas, just outside Rome. With her, she brings the couple's infant son. In front of his people (including wife Calpurnia), Cleopatra declares that Caesar is her son's father, publicly forcing his hand, and demanding that her son be allowed to rule both Egypt and Rome invoking the consternation of Brutus and Cassius.
Although he accepts Caesarion as his child, Caesar denies the queen's request, explaining that Egypt is only free from Rome because he wishes it to be. Just before her return to Egypt, Cleopatra soon learns that Caesar has been assassinated at the hands of Brutus, Cassius and other senators. The burdens of ruling fall on the shoulders of Caesar's Roman heir and nephew, Octavian. With his ascendancy, Octavian and his friend Mark Antony have a war against Brutus and Cassius. In the process, both Cassius and Brutus commit suicide. This means Octavian's forces win.
Octavian also plans to rid himself of his rival, Cleopatra's baby boy, Caesarion, who, as Caesar's only child, threatens his reign. Renaming himself Caesar Augustus, Octavian sends soldiers to Egypt to find and kill Caesar's son. In the meantime, Antony is sent to Alexandria to protect Caesarion and Queen Cleopatra. In spending time with together, Antony and Cleopatra fall in love. Although they wish to marry, Antony reveals that he wed Octavian's sister, Octavia, in order to strengthen his alliance and co-ruling with the new emperor. Defying his Roman beliefs against polygamy, Antony marries Cleopatra in Antioch, claiming that her son, Caesarion, is heir to not only Egypt, but also Rome.
Upon hearing of Antony's claim, Octavian wages war against the two lovers, trapping Cleopatra in her own city. Threatening suicide if Octavian does not let her son go, Cleopatra learns that she has lost Antony, who killed himself in battle after losing to Octavian's army. Octavian arrives in Egypt, demanding that Cleopatra join him in Rome as his prisoner. She refuses and demands that her son be allowed to rule Egypt. Octavian does not agree to this, but allows Antony to have an Egyptian burial. After sending her son to India, Cleopatra's plan goes through, as she has an asp in a basket of figs brought to her heavily guarded tomb. There, she lets the asp bite her, and dies shortly after. Her handmaidens quickly follow their queen's example. Octavian's men break through the doors, only to discover that the queen is dead. After they discover that Cleopatra is dead, Octavian then takes over Egypt about two years later after Cleopatra's death. At the end of the film, Octavian approaches Cleopatra and finds that she is dead. Then he says "You have won, Cleopatra" and then leaves.