Sindh has been known by various names in the past, the name Sindh comes from the Indo-Aryans whose legends claimed that the Indus River flowed from the mouth of a lion or Sinh-ka-bab. In Sanskrit, the province was dubbed Sindhu meaning an ocean. The Assyrians (as early as the seventh century BCE) knew the region as Sinda, the Persians Abisind, the Greeks Sinthus, the Romans Sindus, the Chinese Sintow, while the Arabs dubbed it Sind. Also, in ancient times, the territory of the modern Sindh province was sometimes known as Sovira (or Souveera) and also as Sindhudesh, Sindhu being the original name for Indus river and the suffix 'desh' roughly corresponding to country or territory.
The first known village settlements date as far back as 7000 BCE. Permanent settlements at Mehrgarh to the west expanded into Sindh. The original inhabitants of ancient Sindh, and other regions of the Indian Subcontinent, were the aborigine tribes speaking languages related to Munda languages. The Dravidians migrated from the Iranian plateau and settled in the Indus valley around 4000 BCE. The Dravidian culture blossomed over the centuries and gave rise to the Indus Valley Civilization around 3000 BCE. The Indus Valley Civilization rivalled the contemporary civilizations of Ancient Egypt and Mesopotamia in both size and scope numbering nearly half a million inhabitants at its height with well-planned grid cities and sewer systems. Speculation remains as to how and why the civilization declined and may have been a combination of natural disasters such as flooding and internecine conflicts. The Indus Valley Civilization spanned much of what is today Pakistan and Northwestern India, but suddenly went into decline just prior to the rise of Indo-Iranians. A branch of these tribes called the Indo-Aryans are believed to have founded the Vedic Civilization that have existed between Sarasvati River and Ganges river around 1500 BCE. This civilization helped shape subsequent cultures in the Indian subcontinent.

Sindh was conquered by the Persian Achaemenid Empire in the 6th century BCE, and became part of the Persian satrapy (province) of Hindush centred in the Punjab to the north. Persian speech had a tendency to replace 'S' with an 'H' resulting in 'Sindu' being pronounced and written as 'Hindu'. They introduced the Kharoshti script and links to the west in the region. Subsequently conquered by Greeks led by Alexander the Great, the region came under loose Greek control for a few decades until Alexander's death and brief Seleucid rule and then was conquered by the Mauryans led by Chandragupta in 305 BCE. Later, during the reign of the Buddhist king Ashoka the region would solidly become a Buddhist domain. Following a century of Mauryan rule which ended by 232 BCE, the region came under the Greco-Bactrians based in what is today Afghanistan and these rulers would also convert to and proliferate Buddhism in the region. The Buddhist city of Siraj-ji-Takri is located along the western limestone terraces of the Rohri Hills in the Khairpur district of Upper Sindh, along the road that leads to Sorah. Its ruins are still visible on the top of three different mesas, in the form of stone and mud-brick walls and small mounds, whilst other architectural remains were observed along the slopes of the hills in the 1980s. This city is not mentioned from any text dealing with the history of the Buddhist period of Sindh.