The Indus region which covers much of Pakistan, was the site of several ancient cultures including the Neolithic era Mehrgarh, and the Bronze era Indus Valley Civilization (2500 BCE - 1500 BCE) at Harappa and Mohenjo-Daro.

Waves of conquerors and migrants including Harappan, Indo-Aryan, Persian, Grecian, Saka, Parthian, Kushan, White Hun, Afghan, Arab, Turkics, and Mughal settled in the region throughout the centuries, influencing the locals and being absorbed among them. However, while the eastern provinces of Punjab and Sind became aligned with Indo-Islamic civilization, the western areas became culturally allied with the Iranic civilization of Afghanistan and Iran.

The modern state of Pakistan was established on 14 August 1947. The region is a crossroads of historic trade routes, including the Silk Road. The Indus Valley Civilization collapsed in the middle of the second millennium BCE and was followed by the Vedic Civilization, which extended over much of the Indo-Gangetic plains.

Successive empires and kingdoms ruled the region from the Achaemenid Persian empire around 543 BCE, to Alexander the Great in 326 BCE and the Mauryan empire. The Indo-Greek Kingdom founded by Demetrius of Bactria included Gandhara and Punjab from 184 BCE, and reached its greatest extent under Menander, establishing the Greco-Buddhist period with advances in trade and culture.

The city of Taxila (Takshashila) became a major centre of learning in ancient times - the remains of the city, located to the west of Islamabad, are one of the country's major archaeological sites.