The earliest evidence of man on Spetses comes in the shape of two Mesolithic flint spear-heads. These were discovered at Zogheria, and are thought to indicate a passing visit by hunters from the Fraghthi cave on the mainland who were searching for water. Spetses' first inhabitants appear to have been mostly just passing through, on their way from the Peloponnese to the Cyclades.

We also know that around 1170BC, towards the end of the Mycenaean Era, the island was attacked by Mycenaean forces. It is considered a good possibility that ancient inhabitants of Spetses fought in the historic battle at Salamis, and that the island was attacked by Athenians during the Peloponnesian War.

Having passed through periods as a naval base for mainland cities, and as a part of the Roman Empire, along with the rest of Greece, Spetses was among the coastal areas left desolate by repeated pirate invasions. It is believed most likely that the majority of the islands inhabitants at this point in time sought refuge in the Roman-ensured safety of coastal towns on the Peloponnese.