The Indus River is the longest and most important river in Pakistan. It is the longest river and the third largest river, in terms of annual flow, in the Indian subcontinent. The British used the name 'India' for the entire subcontinent based on the appellation of this river. Originating in the Tibetan plateau in the vicinity of Lake Mansarovar, the river runs a course through Ladakh district of Jammu & Kashmir and Northern Areas, flowing through the North in a southerly direction along the entire length of the country, to merge into the Arabian Sea near Pakistan's port city Karachi. The total length of the river is 3,180 kilometres (1,976 miles). The river has a total drainage area exceeding 1,165,000 square kilometres (450,000 square miles). The river's estimated annual flow stands at around 207 cubic kilometres. Beginning at the heights of the world with glaciers, the river feeds the ecosystem of temperate forests, plains and arid countryside. Together with the rivers Chenab, Ravi, Sutlej, Jhelum, Beas and the extinct Sarasvati River, the Indus forms the Sapta Sindhu ("Seven Rivers") delta in the Sindh province of Pakistan. It has 20 major tributaries.

The Indus provides the key water resources for the economy of Pakistan - especially the breadbasket of Punjab province, which accounts for most of the nation's agricultural production, and Sindh. The word "Punjab" is a combination of the Persian words 'panj' (پنج) Five, and 'āb' (آب) Water, giving the literal meaning of the Land of the Five Rivers. The five rivers after which Punjab is named are the Beas, Jhelum, Chenab, Ravi and Sutlej. The river also supports many heavy industries and provides the main supply of potable water in Pakistan.

The ultimate source of the Indus is in Tibet; it begins at the confluence of the Sengge and Gar rivers that drain the Nganglong Kangri and Gangdise Shan mountain ranges. The Indus then flows northwest through Ladakh-Baltistan into Gilgit, just south of the Karakoram range. The Shyok, Shigar and Gilgit streams carry glacial waters into the main river. It gradually bends to the south, coming out of the hills between Peshawar and Rawalpindi. The Indus passes gigantic gorges 4,500-5,200 metres (15,000-17,000 feet) high near the Nanga Parbat massif. It swiftly flows across Hazara, and is dammed at the Tarbela Reservoir. The Kabul River joins it near Attock. The remainder of its route to the sea is in plains of the Punjab and Sind, and the river becomes slow-flowing and highly braided. It is joined by Panjnad River at Mithankot. Beyond this confluence, the river, at one time, was named Satnad River (sat = seven, nadi = river), as the river was now carrying the waters of Kabul River, Indus River and the five Punjab rivers. Passing by Jamshoro, it ends in a large delta to the east of Thatta.

The Indus is one of the few rivers in the world that exhibit a tidal bore. The Indus system is largely fed by the snows and glaciers of the Karakoram, Hindu Kush and Himalayan ranges of Tibet, Kashmir and Northern Areas of Pakistan. The flow of the river is also determined by the seasons - it diminishes greatly in the winter, while flooding its banks in the monsoon months from July to September. There is also evidence of a steady shift in the course of the river since prehistoric times - it deviated westwards from flowing into the Rann of Kutch.