Cleopatra was never in fact the sole ruler of Egypt; she only co-ruled with her father, brother, brother-husband, and son. However, in all these cases, Cleopatra was the true ruler.

Cleopatra VII was Greek and born in Alexandria, Egypt, took the throne alone at the death of her father Ptolemy XII in spring 51 BC. She was at the time the oldest child of Auletes, since two older sisters had died. She also had one younger sister whose name was Arsinoë.

In 48 BC, the advisors of Ptolemy XIII, led by the eunuch Pothinus, removed Cleopatra's power and forced her to flee Egypt. Her sister Arsinoë accompanied her. Later that year, however, Ptolemy imperiled his own power by injudiciously meddling in the affairs of Rome.

When Pompey, fleeing the victorious Julius Caesar, arrived in Alexandria seeking sanctuary, Ptolemy had him murdered in order to ingratiate himself with Caesar. Caesar was so repelled by this treachery that he seized the Egyptian capital and imposed himself as arbiter between the rival claims of Ptolemy and Cleopatra. After a short war, Ptolemy XIII was killed and Caesar restored Cleopatra to her throne, with Ptolemy XIV as new co-ruler.

Caesar wintered in Egypt in 48 BC–47 BC, and Cleopatra became his lover. Egypt remained independent, but three Roman legions were left to protect it. Cleopatra's winter liaison with Caesar produced a son whom they named Ptolemy Caesar (nicknamed Caesarion, little Caesar). However, Caesar refused to make the boy his heir, naming his grand-nephew Octavian instead.

Cleopatra and Caesarion visited Rome between 46 BC and 44 BC and were present when Caesar was assassinated. Before or just after she returned to Egypt, Ptolemy XIV died mysteriously. Cleopatra then made Caesarion her co-regent. She may have poisoned her brother.

In 42 BC, Mark Antony, one of the triumvirs who ruled Rome in the power vacuum following Caesar's death, summoned Cleopatra to meet him in Tarsus to answer questions about her loyalty. Cleopatra arrived in great state, and so charmed Antony that he chose to spend the winter of 42 BC–41 BC with her in Alexandria.

Four years later, in 37 BC, Antony visited Alexandria again while en route to make war with the Parthians. He renewed his relationship with Cleopatra, and from this point on Alexandria would be his home. He may have married Cleopatra according to the Egyptian rite although he was, at the time, married to Octavia, sister of his fellow triumvir Octavian.

Octavian convinced the senate to levy war against Egypt. Antony and Cleopatra were defeated at the battle of Actium and retreated to Alexandria, where they committed suicide when Octavian invaded.

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