In recent discoveries, archaeologists have found artifacts dating back to the Palaeolithic, Mesolithic, Neolithic, Bronze and Iron ages.

Over the course of the Elamite civilization (2700 - 1600 BC) Isfahan emerged gradually under the name of Aspandana also spelt Ispandana. During the Median dynasty steadily grew into a noteworthy regional center that benefited from the exceptionally fertile soil on the banks of the Zayendehrud River. Once Cyrus the Great unified Persian and Median lands into the Achaemenid Empire (648 - 330 BC), the religiously and ethnically diverse city of Isfahan became an early example of the king's fabled religious tolerance. The Parthians (250 BC - 226 AD) continued this tradition after the fall of the Achaemenids, fostering the Hellenistic dimension within Iranian culture and political organization introduced by Alexander's invading armies.
At the time of the next empire to rule Persia, the Sassanids (226 - 652 AD), the city was called by the name Spahān in Middle Persian. The city was governed by "Espoohrans" or the members of seven noble Iranian families who had important royal positions, and served as the residence of these noble families as well.

In 1598 Shah Abbas the Great moved his capital from Qazvin to the more central and Persian Isfahan, called Ispahān in early New Persian so that it wouldn't be threatened by his arch rival, the Ottomans. This new importance ushered in a golden age for the city, with architecture, prestige, and Persian culture flourishing.

Today Isfahan is the third largest city in Iran.