Sutlej River is the longest of the five rivers that flow through the historic cross-road region known as the Punjab in northern India as well as Pakistan, and is located North of the Vindhya range, south of the Hindu Kush segment of the Himalayas, and east of the Central Makran range in Pakistan. Its source is in Tibet near Mount Kailash and its terminus in Pakistani Punjab near the port city of Karachi via the Indus.

It is the easternmost tributary river of the Indus River, which overall, drains the Greater (ancient and historically important region of) Punjab. Located in the shadow of the Vindhya range, the region to its south and east is arid and known in different regions as the Great Indian Desert or Thar Desert, which more or less parallels both the river and the border between Pakistan and Rajistan. Flowing generally South-south-west from its headwaters, it joins first with the Beas River in the state of Punjab, India and continues south-westerly into Pakistan to mix with the Chenab River forming the Panjnad River south of ancient Multan. From the confluence near Khanpur, the Panjnad joins the Indus River at Mithankot, whereafter the large river flows through a gorge near Sukkur and flows through a fertile plains region known as the Sind until it reaches the Arabian sea.

The Sutlej was known as Shatadru to Indians in Vedic period.

Sutlej Valley from Rampur ca. 1857A heavy freight canal, known as the SLY (Sutlej-Yamuna Link), is being built eastwards through Punjab near an ancient caravan route and highlands pass from the Sutlej watershed to connect near the source of the largest tributary of the Ganges, the Yamuna river, and when complete will allow shipping from India's east coast to the west coast.