Alexander the Great seized Egypt in 332 B.C. Egypt was a theocracy with religion and state combined, and Alexander sought to maintain this relationship to gain the support from the native bureaucracy. He even permitted the native satrap, Mazaces, to retain his position, wealth and lands. However Ptolemy I gained the position of satrap in 325 B.C. and demoted the previous satrap, actually Cleomenes. Cleomenes was assassinated, and Ptolemy I consolidated his position. Alexandria, the city established by Alexander the Great, became a center of commercial and political operations in Egypt under Ptolemy I. Ptolemy had further sought to consolidate his position with a new cult of Sarapis, which failed. His successor, Ptolemy II Philadelphus, was school in a variety of subjects including zoology and geometry by a group of tutors beginning with Philetas of Cos. Under the reign of Ptolemy I and Ptolemy II the famous Museum and Library of Alexandria were founded and constructed. Scholarly and scientific learning continued and prospered undiminished throughout the Hellenistic era.

His successor, Ptolemy III, introduced bronze coinage in the form of bronze, after silver coinage had been previously introduced. During his reign the famous Erastosthenes of Cyrene, the librarian in Alexandria, measured the circumference of the Earth. Ptolemy IV succeeded Ptolemy III in 221 B.C. and during his reign Ptolemaic Egypt fell into a chaotic decline, that ended with its conquest by Rome at the battle of Actium in 27 B.C. Upper Egypt was lost to Ptolemy IV along with its revenue.

Ptolemaic Egypt had egaged in internecine warfare with rival states to the south in Africa, Coele-Syria of the Seleukids, before it was subdued by Rome. Its monarchs were very isolated from even the Hellenic elite, and even engaged in the traditional Egyptian practice of incestual marriage of brother and sister to keep the royal bloodline pure. There were numerous court intrigues and killings to usurp or protect one's power within the court or take power from the throne. Ptolemy II had his brother, Argaeus, executed for conspiring against him. Arsinoë II Philadelphus(loving-her-brother) married her own brother and bore children to him.

Rome's power became paramount over Egypt, when Ptolemy X Alexander I gave Egypt to Rome in his will in 87 B.C. However Rome decided not to take Egypt, because it had fallen into civil war. In 80 B.C. the first puppet to Rome, Ptolemy XI Alexander II, worked for the Roman general, Sulla. There was a great deal more of court intrigue until Cleopatra VII triumped. She realized the growing influence of Rome from 60 to 52 B.C. and conspired with Roman generals against Rome. Finally her forces combined with the forces of the Roman general, Anthony, were destroyed in 27 B.C. at Actium and ended the Hellenistic era.