Before its colonial incarnation, the seven islands of Bombay were home to Koli fisherfolk who migrated from Gujarat. Their shanties still occupy parts of the city's shoreline today. In the 2nd century BC the nearby island of Salsette was occupied by the Buddhist Satvahanas who began construction of Kanheri Caves. The seven islands-Mahim, Worli, Parel, Mazagaon, Old Woman's Island, Colaba and Bombay Island itself were known as Heptanesia to the Romans, and Pliny and Ptolemy recorded Roman and Persian trade with ports in the vicinity.

The islands were ruled by a succession of Hindu dynasties, including the Chalukyas who swept down from their Deccan stronghold to establish a capital on Gharapuri (now known as Elephanta Island) around the 6th century AD. They built the magnificent Shiva cave temple on the island that is one of the few UNESCO World Heritage sites in India today. The Silharas from the Konkan coast established capitals on Gharapuri and at nearby Thane in the 9th century. They occupied Malabar Hill in the II th century, building the Walkeshwar Temple on Malabar Point. In the 12th century Raja Bhimdev established a Hindu kingdom on Mahim, which became the first of the seven islands to support a population of any size.

The islands were invaded by Muslims in the 14th century and passed between the Sultans of Gujarat, Delhi and the Deccan as their influence in the region waxed and waned. The Portuguese first raided the area in 1508, when Dom Francisco Almeida, the inaugural Viceroy of Goa, seized a Gujarati ship in Mahim Creek. Their incursions increased over the next three decades until Bassein and the inconsequential islands of Bombay were ceded to Portugal in 1534 by the Sultan of Gujarat, Bahadur Shah. The sultan hoped to form an alliance with the Portuguese that would prevent Mughal incursions into Gujarat.