One hypothesis is that the device was constructed at an academy founded by the ancient Stoic philosopher Posidonius on the Greek island of Rhodes, which at the time was known as a centre of astronomy and mechanical engineering.

As the new finds of the Antikythera Mechanism Research Project suggest that it was made around 150 to 100 BC, well before the time of Posidonius, it is possible that the great astronomer Hipparchus was the genius engineer who constructed it. Hipparchus was the most important astronomer of that time and worked for a long period in Rhodes, Greece. The Mechanism contains a lunar mechanism which uses Hipparchus' theory for the motion of the Moon and this also suggests strong ties of the Mechanism to Hipparchus.

It is possible that the mechanism is based on heliocentric principles, rather than the then-dominant geocentric view espoused by Aristotle and others. The heliocentric view proposed by Aristarchus of Samos (310 BC - c. 230 BC) did not receive widespread recognition, but provides for the possibility of the existence of such a system at this time.