The story commences in the midst of Roman civil war where the Great Julius Caesar (Rex Harrison) has just defeated his nemesis, his daughter's husband, Pompei, and his troops. Sadly, however, the victory is won with a bittersweet ambivalence for the noble Caesar. In search of nemesis, Caesar discovers Pompei to have slipped past Roman forces and traveled to Egypt. Thus, deciding to venture to Egypt to approach Pompei, Caesar enlists his head soldier, Marc Antony (Richard Burton), as his authoritative voice in lieu of his hiatus to Egypt. There, however, Caesar discovers that so too is Egypt in a state of crisis. Civil war seems contagious enough as Cleopatra's brother Ptolemy, in his desire to have sole leadership of the throne, has driven Cleopatra (Elizabeth Taylor) to the coastal town of Alexandria as he further plots her demise with the help of his cunning associate Flavius.

As Caesar and his men set foot on Egyptian soil they are greeted, not so hospitably, by Ptolemy and his troupe of servants, advisors, and generals. Immediately Caesar sees Ptolemy for what he is: a sniveling, spoiled, ignorant, selfish child greedy for sole power for the throne and who attempts to attain it by any means necessary, means which in his unripe age he has not yet fully comprehended the magnitude of their repercussions. As Ptolemy and his associate try to dance around Caesar's straightforward requests they ignorantly present to him Pompei's head, believing it to be an honored gift which would sway his allegiance to their mercies. Of course their disrespectful and selfish actions only anger Caesar and he immediately orders quarters and sends summons to Cleopatra.

Arriving in 'royal' fashion, Cleopatra tumbles out of a grand Persian rug where she immediately insists on Caesar's assisting her obtain sole power of the throne as is best for Egypt. Disliking her odious brother Ptolemy and his paratroop of villains, Caesar agrees to protect Cleopatra from her brother, and possibly aiding her quest to Queenship so long as she continues to loyally supply Rome with their required provisions such as grain and riches. As a sexually laden banter ensues between the two power hungry authorities, a passion between the two erupts into a passionate undercover love affair.

Cleopatra by an accidentally fortunate discovery of Ptolemy and Flavius' attempts to poison her, observed in the unfortunate fate of her handmaid, is suddenly granted her greatest wish. Caesar seeks out her culprit and sentences him to death; so too does he release Ptolemy from Rome's protection and sends him to his doomed death by stationing him in the precarious army led by Achilles which, coincidentally, happens to be caught between a rock and a hard place in their war efforts. Thus, in a matter of days Caesar provides Cleopatra with a confidant and the sole ruler-ship of Egypt.

So as to thank him for his advantageous presence, Cleopatra promises to bear Julius a son as their relationship grows more intimate. But a lover's quarrel is more volatile than an indifferent dispute and when Cleopatra asks Caesar to honor the late Great Alexander's vision with the powerful alliance of Egypt and Rome, Caesar, unfortunately, hesitantly acquiesces and rumor spreads that Caesar and Cleopatra have wed and the former was declared an Egyptian God, much to the demise of his barren wife back home in Rome who immediately tells Antony of the conspiracy. Soon enough Cleopatra bears his son and, as King and Queen of Egypt, head General of Rome, and father of the future heir to Rome and Egypt, his son Caesarian, Caesar remains in Egypt where he happily lives out the early days of his new fatherhood with his beautiful wife.

Meanwhile, back in Rome, the Senate, lead by Cicero, pontificates the precarious position Caesar has placed Rome in. Marc Antony however, remains loyally supportive of his lord's decisions. But soon enough Caesar upholds his patriotic duties and heads for home, which he doesn't reach until another 2 years of imperialistic venture through the African continent and foreign locales of Italy. Only then does Caesar return home to Rome and enters the city where, within a year, he earns the title as 'Dictator for Life' of Rome. While Caesar's other loyal soldier, Rufio (Martin Landau), explains to Cleopatra that the dictator's power is always checked by the Senate in the Republic system of government, the hasty woman puts a hiatus on her urgent desire to head to her allied city and return to her husband. Nevertheless, soon enough Cleopatra and her son make their way through the Roman gates in a grandeur parade of trumpets, sirens, mares, multi colored exotic spectacles. And of course, the most elaborate Egyptian chariot contrived. And just as she arrives in an overtly Grande fashion, so too does Cleopatra immediately humble herself, most advantageously, before her husband and instantly win the loyalty of the Roman public.

But though Caesar is a favorite, and his wife a favorite with the public, together the two grow more and more precarious in the opinions of the Roman Senate, particularly when Caesar requests his being granted the title of Emperor. As the Senate deliberates over Caesar's request, turning to Brutus for help in upholding Rome's honor, so too do they observe how Caesar's sickness and age grows. As an empty gesture the Senate attempts to offer the title of kingship to Caesar, king that is, over the entire Roman Empire, save for the city of Rome itself. But with the persistent support of Cleopatra and Marc Antony, Caesar decides to accept the title all the while unknowing that the Senate plots his death. As both of his wives, Roman and Egyptian alike, attempt to persuade him to avoid the Senate meeting the following day, the strong-willed man attempts to dissuade superstition and prepares to accept his expected title. Of course what he does receive however is not kingship, but death, and Cleopatra and her son Caesarian are left to comfort their grief in the solace of each other's company in Egypt, forced to flee Rome while Marc Antony does his best to restore order to the troubled Empire.

For two years Antony goes in search of the villainous Senate members and, afterwards, becomes the succeeding Caesar. Unfortunately alongside the noble Antony are the traitorous Agrippa (Andrew Keir), and the next heir to the title of Caesar, Augustus Octavian (Roddy McDowell). A calculated decision results in a tripartite rule of the Roman Emperor: Octavian to rule the center, Lepidus to rule Africa, and Antony to rule the rest. Quickly then, Antony makes way to Egypt where he will attempt to once again persuade Cleopatra into allying with Rome.

What results next, is the notorious love affair between her Majesty and her ex-husband's most revered soldier. As the two engage in an illicit affair, much to the disapproval of the Roman Senate, and eventually the Roman public, Antony will struggle with accepting a change in fate that will not see his total dictatorship over the Roman Empire. From revered soldier and newfound heir to the Roman title of Caesar, Antony grapples with seceding his power to the nefarious Roman Octavian in exchange for his love of Cleopatra. Though Octavian attempts to solidify Antony's alliance with Rome via his marriage to Octavian's sister, Octavia, it isn't long before the lackluster Antony abandons his home country to return to his Egyptian Queen. But there, his alliances and his illicit affair with the Queen spark heavy disdain from the Roman Senate who quickly declare war on their traitorous 'citizen'.

Once again Rome finds itself at Civil War by sea as Antony and his minute legion of loyal Roman troops do their best to defeat the massive troop of Octavian's men stationed in battle war ready ships. Outnumbered 20 to 1, Antony nobly heads out to sea where he will face his inevitable defeat in the infamous battle of Actium, Greece. Quickly Antony is assumed dead as the Roman troops attack head on, leaving a despairing Cleopatra with no other option than to once again flee back to her beloved Egypt. Still alive however, a heartbroken Antony forgets all of war and jumps on the nearest escape boat and heads for his lover's vessel. But once there, Antony has time to reflect on his shameful abandonment of his troops, his un-Roman-like betrayal to his men, his cowardice, etc.

Cleopatra and Athony's loyal assistant, Rufio, attempt to persuade Antony to lead the Egyptian's defense against the infiltrating Romans; to no avail. But as Octavian and his men encroach, Antony, for the sake of love, decides to once again assume the position of head General; this time with the Egyptian army. But while restlessly slumbering before the great day of war Antony will awake to find his troops half-slaughtered, half abandoned camp, and his loyal servant Rufio dead on the stained ground. As he rides out to Caesar Octavian prepared to die a noble death, Antony is half enraged, half ashamed to find an indifferent troop of betraying fellow Roman soldiers. Meanwhile Octavian's men have intercepted Caesarian, Cleopatra and Julius Caesar's son, and have slain him as a result of preserving Octavian's rule.