The harbour lies between the Lyari River delta and Chinna Creek to the north, and the Arabian Sea to the south.

Karachi is also mentioned in the sixteenth century Turkish treatise Mir'ât ül Memâlik (Mirror of Countries, 1557) by the Ottoman captain Seydi Ali Reis, which warns sailors about whirlpools and advises them to seek safety in "Kaurashi" harbour if they found themselves drifting dangerously.

[11][12][13] In 1728 heavy rains silted up the harbour at Kharak, forcing merchants to relocate to the area of modern Karachi.

[14] In 1725, a band of Balochi settlers from Makran and Kalat had settled in the hamlet after fleeing droughts and tribal feuds.

In 1783, after two prolonged sieges the town fell to the Talpur Mirs of Sind, who constructed a fort mounted with cannons on Manora island at the harbour entrance.

[20] At the outbreak of the American Civil War, Karachi Harbour became an important cotton-exporting port,[21] with Indus Steam Flotilla and Orient Inland Steam Navigation Company established to transport cotton from interior Sindh to the harbour, and onwards to textile mills in England.

[26] Manora is a small peninsula that forms a protective barrier between Karachi Harbour to the north and the Arabian Sea to the south.

[27] was formerly an island, but due to silting is now connected to the mainland by a 12 kilometres (7.5 mi) long natural sandbridge known as Sandspit.

The entrance to Karachi was once guarded against pirate raids by the Manora Fort built in the 1790s, which was later upgraded by the British, and then the Pakistan Navy.