Alexander's invasion had a two-fold political effect: By crushing the Achaemenian Empire it loosened the already feeble control of the Persians over Pakistan; and by creating a power vacuum in this area it encouraged, for the first time in history, intrusion by India into Pakistan. Fortunately for India, at this opportune moment a man from Punjab, Chandragupta Maurya, was able to set up a strong government in the Gangetic Valley which extended its sway over most of northern India. Alexander's successor Seleucus who had yet to grid his loins and muster his forces after the Dictator's sudden and unexpected demise, was prevailed upon by diplomacy to cede Pakistan to Chandragupta peacefully, avoiding the sufferings of war whose outcome seemed uncertain to him. Pakistan, as such, became a part of India's Maurya Empire in 300 BC without war. This was the first time in history that Pakistan was looking eastward and the first time it had become part of India and ruled by India. But strangely indeed, shortly afterwards, the third Mauryan Emperor, Asoka, became Buddhist and Pakistan did not have to smart under Hinduism for long. Though incorporated in the Indian Empire, Pakistan escaped Hindu rule. Under Asoka's missionary activities she adopted Buddhism and was to remain largely Buddhist till the arrival of Muslims.

Mauryan rule, however, did not last long. Pakistan's ties with India were severed barely a hundred years later in about 200 BC when the Greek King Demetrius, already in control of the areas beyond Hindu Kush with his capital at Bactria (Balkh in northern Afghanistan), pounced upon Pakistan at the very first opportunity. Within a few years (190-180 BC) Demetrius took over a considerable portion of the Indus basin. This ushered in the golden period of Graeco-Bactrians who had their capital in Taxila. This new state also embraced almost the whole of present day Pakistan within its eastern boundary extending up to Sutlej; had an independent existance and again looked westward having hardly anything to do with India. The greatest Graeco-Bactrian king was Menander who was a Buddhist and ruled from 160-140 BC.