After Alexander left Egypt the city, Cleomenes, continued the creation of Alexandria. With the breakup of the empire on Alexander's death in 323, control of the city passed to his viceroy, Ptolemy I Soter, who founded the dynasty that took his name. The early Ptolemies successfully blended the religions of ancient Greece and Egypt in the cult of Sarapis and presided over Alexandria's golden age.

Alexandria profited from the demise of Phoenician power after Alexander sacked Tyre (332 BC) and from Europe's growing trade with the East via the Nile and the canal that then linked it with the Red Sea. Indeed, Alexandria became, within a century of its founding, the greatest city in the world and a centre of Greek scholarship and science. Such scholars as Euclid, Archimedes, Plotinus the philosopher, and Ptolemy and Eratosthenes the geographers studied at the Mouseion, the great research institute founded by the Ptolemies. Alexandria also was a centre of Jewish learning; and, according to tradition, the Septuagint translation of the Old Testament from Hebrew to Greek was produced there.