In the Shahnameh, Sistan is also referred to as Zabulistan, after Zabul, originally a pure Tajik (Persian) province. In Ferdowsi's epic, Zabulistan is in turn described to be the homeland of the mythological hero-king Rostam.
Alexander's Empire fragmented after his death, and Arachosia came under control of the Seleucid Empire, which traded it to the Mauryan dynasty of India in 305 BC. After the fall of the Mauryans, the region fell to their Greco-Bactrian allies in 180 BC, before breaking away and becoming part of the Indo-Greek Kingdom.
After the mid 100s BC, much of the Indo-Greek Kingdom was overrun by tribes known as the Indo-Scythians or Sakas, from which Sistan (from Sakastan) eventually derived its name. The Indo-Scythians were defeated around 100 BC by the Parthian Empire, which briefly lost the region to its Suren vassals (the Indo-Parthian) around 20 AD, before the region was conquered by the Kushan Empire in the mid 1st century AD. The Kushans were defeated by the Sassanid Persian Empire in the mid 3rd century, first becoming part of a vassal Kushansha state, before being overrun by the Hephthalites in the mid 400s. Sassanid armies reconquered Sistan in by 565 AD, but lost the area to the Arab Rashidun Caliphate after the mid 640s. (For Sistan's history after the Islamic conquest, see History sections of Afghanistan and Iran).
The Saffarids (861-1003 CE), one of the early Iranian dynasties of the Islamic era, were originally rulers of Sistan.
Sistan has a very strong connection with Zoroastrianism and during Sassanid times Lake Hamun was one of two pilgrimage sites for followers of that religion. In Zoroastrian tradition, the lake is the keeper of Zoroaster's seed and just before the final renovation of the world, three maidens will enter the lake, each then giving birth to the saoshyans who will be the saviours of mankind at the final renovation of the world.
The most famous archaeological site in Sistan is on Kuh-e Khwajeh, a hill rising up as an island in the middle of Lake Hamun.